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the percentage of participants achieving complete response (CR) or partial response (PR) was 6x higher in the HER2-positive group in the primary trial, than in the ER+ and/or PR+ group. | Outcome Measurement:
CNS Objective Response Rate (ORR)
The central nervous system (CNS) ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria in the evaluation CNS lesions on treatment: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Disease assessments occurred every 6 cycles. Patients with stable or responsive disease after completion of 6 cycles could reduce frequency of assessments to every 3 cycles. Response was evaluated up to 25 months.
Results 1:
Arm/Group Title: Cohort 1 - Cabozantinib, Trastuzumab for HER2+
Arm/Group Description: HER2-positive
Cabozantinib- orally administered daily per treatment cycle
Trastuzumab- IV administered once per cycle
MRI- Baseline, Cycle 2 Day 1, and every 2 cycles
Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1,
Cabozantinib: One, 60 mg tablet daily of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Trastuzumab: For HER2-Positive participants only. Administered by IV on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Overall Number of Participants Analyzed: 21
Measure Type: Number
Unit of Measure: percentage of participants 5 (.2 to 24)
Results 2:
Arm/Group Title: Cohort 2 - Cabozantinib for ER+ and/or PR+
Arm/Group Description: Hormone receptor-positive (ER+ and/or PR+)
Cabozantinib- orally administered daily per treatment cycle
MRI- Baseline, Cycle 2 Day 1, and every 2 cycles
Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1,
Cabozantinib: One, 60 mg tablet daily of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Overall Number of Participants Analyzed: 7
Measure Type: Number
Unit of Measure: percentage of participants 14 (.4 to 58) | Contradiction |
In total Less than 10% of patients in the primary trial either had a disease relapse or died. | Outcome Measurement:
Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years
Number of events (disease relapse or death) to time of observation for DFS. DFS defined as time from randomization to earliest documentation of disease relapse or death from any cause in postmenopausal, receptor positive, node negative or node positive breast cancer patients for adjuvant treatment with exemestane compared with adjuvant tamoxifen therapy at 2.75 years. Disease relapse: primary tumor recurrence (locoregional or distant) and ipsilateral or contralateral breast cancer (CBC). Intercurrent death: death without disease relapse.
Time frame: Baseline (Month 0) up to 2.75 years
Results 1:
Arm/Group Title: Exemestane
Arm/Group Description: Exemestane (Aromasin ) 25 mg QD for 5 years.
Overall Number of Participants Analyzed: 4898
Measure Type: Number
Unit of Measure: Events (disease relapse or death) 352
Results 2:
Arm/Group Title: Tamoxifen Followed by Exemestane
Arm/Group Description: Tamoxifen 20 mg QD; upon completing 2.5 years to 3 years of tamoxifen, participants were to be switched to exemestane 25 mg QD and then were to complete a total of 5 years endocrine therapy.
Overall Number of Participants Analyzed: 4868
Measure Type: Number
Unit of Measure: Events (disease relapse or death) 388 | Entailment |
Patients currently prescribed Diuretics are excluded from the primary trial. | Exclusion Criteria:
medication(s) known to affect body fluid balance | Entailment |
Unlike the primary trial, the secondary trial does not test Gonadotrophin-releasing Hormone Analogues or medical devices. | INTERVENTION 1:
Pecs Group
Ultrasound guided pectoral nerve block is performed right after induction, before surgery. The needle is advanced to the tissue plane between the pectoralis major and pectoralis minor muscle at the vicinity of the pectoral branch of the acromiothoracic artery, and 10 mL of 0.5% ropivacaine deposited. In a similar manner, 20 mL is deposited at the level of the third rib between the pectoralis minor muscle and the serratus anterior muscle .
INTERVENTION 2:
Control Group
There is no block.
INTERVENTION 1:
Tamoxifen or Letrozole
tamoxifen or letrozole work in treating women with ductal carcinoma in situ
letrozole
tamoxifen citrate
conventional surgery
neoadjuvant therapy | Contradiction |
There were 4% more cases (1 more case) of Dyspnea than Dehydration in the primary trial. | Dehydration 1/25 (4.00%)
Dyspnea (Shortness Of Breath) 2/25 (8.00%) | Entailment |
The intervention in the primary trial requires patients to receive multiple applications of treatment over a period of several weeks, whereas the interventions for the secondary trial are only apllied once. | INTERVENTION 1:
0.005% Estriol Vaginal Gel
Route: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
INTERVENTION 1:
One-port
intervention is placement of one-port tissue expander at time of reconstruction
Allergen one-port tissue expander placement: patients will be randomized to receive a one port or two port tissue expander for breast reconstruction | Entailment |
The median TTP for patients in cohort one of the primary trial is NA. | Outcome Measurement:
Time to Progression (TTP)
Time to progression is defined as the time from treatment start until objective tumor progression. Progression is defined per Response Evaluation Criteria in Solid Tumors (RECIST)v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. The median time to progression is the parameter used to describe TTP.
Time frame: TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), up to 29 months.
Results 1:
Arm/Group Title: Capecitabine and Fulvestrant
Arm/Group Description: Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po AM and 500 mg po PM in patients of body weight < 80 kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of 80 kg.
Fulvestrant will be given at 500 mg on Day 1 followed by 250 mg on Days 15 and 29, then 250 mg every 28 days.
Overall Number of Participants Analyzed: 41
Median (95% Confidence Interval)
Unit of Measure: Months 26.94 [1] (7.26 to NA) | Contradiction |
There were more cases of embolisms in cohort 2 of the primary trial than cohort 1. | Adverse Events 1:
Total: 111/669 (16.59%)
Leukocytes * [1]1/669 (0.15%)
Hemoglobin * [1]1/669 (0.15%)
Hemoglobin * [2]0/669 (0.00%)
CNS cerebrovascular ischemia * [1]0/669 (0.00%)
CNS cerebrovascular ischemia * [3]0/669 (0.00%)
Heart Failure * [1]3/669 (0.45%)
Thrombosis/embolism * [1]1/669 (0.15%)
Thrombosis/embolism * [3]0/669 (0.00%)
Adverse Events 2:
Total: 138/715 (19.30%)
Leukocytes * [1]0/715 (0.00%)
Hemoglobin * [1]0/715 (0.00%)
Hemoglobin * [2]1/715 (0.14%)
CNS cerebrovascular ischemia * [1]1/715 (0.14%)
CNS cerebrovascular ischemia * [3]1/715 (0.14%)
Heart Failure * [1]1/715 (0.14%)
Thrombosis/embolism * [1]3/715 (0.42%)
Thrombosis/embolism * [3]2/715 (0.28%) | Entailment |
It is not possible for a participant of the primary trial to have a Time to Reach Maximum Plasma Concentration of 16, 17 or 20 hours | Outcome Measurement:
Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
Median Tmax = time for maximum plasma concentration (Cmax) for SU011248, SU012662, and combined SU011248 and SU012662 (total drug); collected C1D2, C2D3. Paired observation.
Time frame: 1, 2, 4, 6, 8, 12, 24 hours postdose | Entailment |
Patients must have a triple negative infiltrating breast carcinoma to participate in the secondary trial or the primary trial. | Eligibility Criteria:
Must have invasive metastatic breast cancer
Tumor must be Her 2/neu 3+ by IHC (must be confirmed by Ohio State University pathology)or positive FISH
Inclusion Criteria:
infiltrating (invasive) HER2-neu-negative or HER2-neu-positive breast cancer. | Contradiction |
There is no radiotherapy or educational part of the intervention used in the primary trial. | INTERVENTION 1:
Tamoxifen or Letrozole
tamoxifen or letrozole work in treating women with ductal carcinoma in situ
letrozole
tamoxifen citrate
conventional surgery
neoadjuvant therapy | Entailment |
the primary trial is testing a radiotherapy intervention whereas the secondary trial is testing a novel hand-held medical device | INTERVENTION 1:
Sole Method
patients will be treated with HDR brachytherapy using Mammosite ML as the sole method for radiation delivery after lumpectomy for breast cancer or DCIS
Mammosite ML: 34 Gy / 10 fractions (3.4 Gy per fraction) 2 fractions / day (separated by at least 6 hours) Delivered in 5 consecutive working days
INTERVENTION 2:
Boost
patients will be treated with HDR brachytherapy using Mammosite ML as a boost technique prior to standard external beam radiation after lumpectomy for breast cancer or DCIS
Mammosite ML: 5-10.2 Gy / 2-3 fractions (3.4 Gy per fraction) 2 fractions / day (separated by at least 6 hours) Delivered in 1-2 days Followed by whole breast radiation (25-28 daily tx)
INTERVENTION 1:
Manual Lymph Drainage
Manual lymph drainage (MLD) treatment 3 times a week for 4 weeks to the lymphedematous upper limb
Manual Lymph Drainage (MLD): MLD is a practitioner-applied manual massage technique designed to decrease limb volume in patients with lymphedema by enhancing movement of lymph fluid, resulting in reductions in interstitial fluid.
INTERVENTION 2:
Negative Pressure
PhysioTouch (negative pressure massage) treatment 3 times a week for 4 weeks to the lymphedematous upper limb
PhysioTouch: The PhysioTouch is a hand-held device that administers negative pressure under the treatment head, and gently pulls the underlying skin and subcutaneous tissue into the suction cup. This suction produces a stretch to the skin and in the subcutaneous tissue space. This action is thought to facilitate lymphatic flow from the interstitium into the lymphatic vessels, and mobilizes the superficial fascia. | Entailment |
The interventions in the primary trial and the secondary trial are similar, as they are testing the same medication, however they are not using the same doses. | INTERVENTION 1:
Molecular Breast Imaging
Molecular breast imaging performed after injection of 4 mCi Tc-99m sestamibi and again after 8 mCi Tc-99m sestamibi.
INTERVENTION 1:
Control Arm
Mail
Standard Reminder Postcard
INTERVENTION 2:
Family Physician Reminder Letter Arm
Mail
Standard Reminder Postcard
Family Physician Reminder Letter | Contradiction |
Less than 1/3 participants in the primary trial treated with Lapatinib achieved Progression-free Survival Rate After 6 months of Study Treatment. | Outcome Measurement:
Investigator-evaluated Crude Progression-free Survival Rate After 12 Weeks of Study Treatment
The PFS rate is defined as the percentage of subjects who have shown no evidence of disease progression or death from any cause following 12 weeks of treatment. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Since there is no independent reviewer, only the investigator response was reported.
Time frame: up to week 12
Results 1:
Arm/Group Title: Lapatinib + Bevacizumab
Arm/Group Description: Lapatinib (1500 mg once daily taken orally) and bevacizumab (10 mg/kg intravenously [IV] every two weeks)
Overall Number of Participants Analyzed: 52
Measure Type: Count of Participants
Unit of Measure: Participants No disease progression by Week 12: 36 69.2%
Disease progression or death by Week 12: 16 30.8% | Contradiction |
There were more allergic reactions observed in cohort 1 of the primary trial than cohort 2. | Adverse Events 1:
Total: 5/95 (5.26%)
Febrile neutropenia 0/95 (0.00%)
Neutropenia 0/95 (0.00%)
Atrial fibrillation 0/95 (0.00%)
Pleuropericarditis 0/95 (0.00%)
Vomiting 0/95 (0.00%)
Pryexia 0/95 (0.00%)
Anaphylactic shock 1/95 (1.05%)
Gastroenteritis 0/95 (0.00%)
Fibula fracture 1/95 (1.05%)
Tibia fracture 1/95 (1.05%)
Intervertebral disc protrusion 0/95 (0.00%)
Adverse Events 2:
Total: 3/20 (15.00%)
Febrile neutropenia 0/20 (0.00%)
Neutropenia 0/20 (0.00%)
Atrial fibrillation 1/20 (5.00%)
Pleuropericarditis 1/20 (5.00%)
Vomiting 0/20 (0.00%)
Pryexia 0/20 (0.00%)
Anaphylactic shock 0/20 (0.00%)
Gastroenteritis 1/20 (5.00%)
Fibula fracture 0/20 (0.00%)
Tibia fracture 0/20 (0.00%) | Entailment |
A female with Hemoglobin > 10.0 g/dl, Absolute neutrophil count 1,733/mm3, platelet count = 100,000/µl and total bilirubin < 1.2 x ULN are eligilbe for the primary trial. | Hemoglobin > 9.0 g/dl
Absolute neutrophil count (ANC) > 1,500/mm3
Platelet count = 100,000/µl
Total bilirubin =1.5 x the upper limit of normal. | Contradiction |
There were no cases of extravasation in either the primary trial or the secondary trial. | Adverse Events 1:
Total: 3/10 (30.00%)
Sinus tachycardia * 1/10 (10.00%)
Blurred vision * 1/10 (10.00%)
Memory impairment * 1/10 (10.00%)
Dyspnea * 2/10 (20.00%)
Adverse Events 1:
Total: 13/24 (54.17%)
FEBRILE NEUTROPENIA 5/24 (20.83%)
HAEMATOTOXICITY 0/24 (0.00%)
NEUTROPENIA 3/24 (12.50%)
LYMPHADENOPATHY 0/24 (0.00%)
PERICARDIAL EFFUSION 1/24 (4.17%)
ATRIAL FIBRILLATION 1/24 (4.17%)
APLASIA 0/24 (0.00%)
NAUSEA 0/24 (0.00%)
PYREXIA 1/24 (4.17%)
EXTRAVASATION 0/24 (0.00%)
CHOLECYSTITIS 1/24 (4.17%)
PATHOLOGICAL FRACTURE 1/24 (4.17%)
Adverse Events 2:
Total: 6/24 (25.00%)
FEBRILE NEUTROPENIA 0/24 (0.00%)
HAEMATOTOXICITY 1/24 (4.17%)
NEUTROPENIA 0/24 (0.00%)
LYMPHADENOPATHY 1/24 (4.17%)
PERICARDIAL EFFUSION 0/24 (0.00%)
ATRIAL FIBRILLATION 0/24 (0.00%)
APLASIA 1/24 (4.17%)
NAUSEA 1/24 (4.17%)
PYREXIA 0/24 (0.00%)
EXTRAVASATION 1/24 (4.17%)
CHOLECYSTITIS 0/24 (0.00%)
PATHOLOGICAL FRACTURE 0/24 (0.00%) | Contradiction |
Women in cohort A and B of the primary trial with serum 25 (OH)D greater than or equal to 30 ng/ml did not receive weekly supplementation of cholecalciferol. | INTERVENTION 1:
Cholecalciferol
Enrolled women received 50,000 IUs weekly supplementation of cholecalciferol for 8 weeks.
INTERVENTION 2:
No Cholecalciferol
Enrolled women with serum 25 (OH)D greater than or equal to 30 ng/ml received no intervention. | Contradiction |
There was twice as many Cardiac adverse events as cases of Dyspnea in cohort 1 of the primary trial. | Adverse Events 1:
Cardiac General, other1/22 (4.55%)
Dyspnea (shortness of breath)2/22 (9.09%) | Contradiction |
In the primary trial Low Dose Magnesium Oxide is 400 mg/day less than high dose Magnesium Oxide. | INTERVENTION 1:
Low Dose Magnesium Oxide (800 mg/Day)
Week 2:
Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Week 3:
Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Weeks 4-9:
Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
INTERVENTION 2:
High Dose Magnesium Oxide (1200 mg/Day)
Week 2:
Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Week 3:
Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Weeks 4-9:
Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD). | Entailment |
the secondary trial and the primary trial are both testing Biodesign interventions. | INTERVENTION 1:
LA-EP2006
During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.
LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
INTERVENTION 2:
Neulasta®
During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.
Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
INTERVENTION 1:
Nipple Reconstruction Cylinder
Nipple reconstruction: Biodesign® Nipple Reconstruction Cylinder | Contradiction |
The patient group with the highest percent of PFS at 5 months in the primary trial was Stage IIIB patients, and the worst was Stage IV Disease patients. | Outcome Measurement:
Event-free Survival
Event-free survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.
Time frame: 11 years
Results 1:
Arm/Group Title: TX/Maintenance Therapy for Stage IIIB/IV Breast Cancer
Arm/Group Description: See Detailed Description.
tamoxifen citrate: Given orally
busulfan: Given orally
thiotepa: Given IV
melphalan: Given IV
aldesleukin: Given SC
sargramostim: Given SC
peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell infusion
radiation therapy: May undergo radiotherapy after completion of IL-2/GM-CSF
Overall Number of Participants Analyzed: 50
Measure Type: Count of Participants
Unit of Measure: Participants Stage IIIB Disease: 18 participants
11 61.1%
Stage IV Disease: 32 participants
9 28.1% | Contradiction |
To be included in the primary trial, patients must have at least 1 unidimensionally measurable lesion, and must meet some specific size conditions. | Measurable disease, defined as >=1 unidimensionally measurable lesion, including >= 1 of the following:
Lesion >= 10 mm on CT scan (5 mm sections)
Lesion >= 20 mm on CT scan or MRI (10 mm sections)
Lesion >= 10 mm on physical exam | Entailment |
Neutropenia was the most common adverse event for patients in cohort 1 of the primary trial. | Adverse Events 1:
Total: 26/69 (37.68%)
Anaemia 2/69 (2.90%)
Febrile neutropenia 3/69 (4.35%)
Neutropenia 4/69 (5.80%)
Cardiac arrest 1/69 (1.45%)
Cardiac failure congestive 1/69 (1.45%)
Cardiac tamponade 1/69 (1.45%)
Pericardial effusion 1/69 (1.45%)
Abdominal pain 1/69 (1.45%)
Ascites 2/69 (2.90%)
Colitis 1/69 (1.45%)
Gastritis 1/69 (1.45%)
Gastritis erosive 1/69 (1.45%) | Entailment |
The same number of cases of Neutropenia and Pancytopenia are observed in patients from cohort 1 of the primary trial. | Adverse Events 1:
Neutropenia * 1/115 (0.87%)
Pancytopenia * 1/115 (0.87%) | Entailment |
Patients with prior radiotherapy for the treatment of stage 4 cancer over 5 years ago, are not eligible for either the primary trial or the secondary trial. | Inclusion Criteria:
Histologically confirmed breast cancer with evidence of metastatic disease
HER2 3+ or FISH (fluorescent in situ hybridization)+
Age 18 years
No prior trastuzumab, except as given in the adjuvant or neoadjuvant setting.
No prior chemotherapy in the metastatic setting.
Exclusion Criteria:
CNS (central nervous system) metastases
Prior radiation therapy within the last 4 weeks
Pregnant (positive pregnancy test) or lactating women
Major surgical procedure, open biopsy, non-healing wounds, or significant traumatic injury within 28 days prior to starting study or anticipation of need for major surgical procedure during the study
Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to start of study.
No prior chemotherapy or radiotherapy | Contradiction |
Black men with and ECOG <=2, with ANC >1.5 x 10^9/L, PLT >100 x 10^9/L and no prior history of blood clots are eligible for the primary trial but excluded from the secondary trial | Inclusion Criteria:
Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Patients must have acceptable organ function, as defined by the following laboratory parameters: white blood count (WBC) >3.0 x 10^9/L; absolute neutrophil count (ANC) >1.5 x 10^9/L; hemoglobin (Hgb) >10.0g/dL; platelets (PLT) >100 x 10^9/L, Bilirubin < 2.0 mg/dl, aspartate aminotransferase/alanine aminotransferase (AST/ALT) < 2.5 X upper limit of normal (ULN), Creatinine <1.8 mg/dl (Creatinine clearance >60 ml/min).
Both men and women of all races and ethnic groups are eligible for this trial.
Patient with a history of blood clots are not eligible.
Inclusion Criteria:
Women of 18 years of age or older. | Entailment |
None of the patients in the primary trial were recorded as having heart related adverse events, whereas many patients in the secondary trial experienced several different heart related issues. | Adverse Events 1:
Total: 6/81 (7.41%)
Colitis [1]1/81 (1.23%)
Multiple Sclerosis Relapse 1/81 (1.23%)
Neurotoxicity [2]2/81 (2.47%)
Community-acquired pneumonia 1/81 (1.23%)
Local Infection Reservoir Area 1/81 (1.23%)
Adverse Events 1:
Total: 20/52 (38.46%)
Anaemia 0/52 (0.00%)
Pancytopenia 1/52 (1.92%)
Acute myocardial infarction 0/52 (0.00%)
Atrial fibrillation 0/52 (0.00%)
Cardiac failure 1/52 (1.92%)
Cardiogenic shock 1/52 (1.92%)
Palpitations 0/52 (0.00%)
Pericardial effusion 0/52 (0.00%)
Right ventricular failure 1/52 (1.92%)
Abdominal pain 0/52 (0.00%)
Ascites 3/52 (5.77%)
Adverse Events 2:
Total: 25/49 (51.02%)
Anaemia 2/49 (4.08%)
Pancytopenia 0/49 (0.00%)
Acute myocardial infarction 1/49 (2.04%)
Atrial fibrillation 1/49 (2.04%)
Cardiac failure 0/49 (0.00%)
Cardiogenic shock 0/49 (0.00%)
Palpitations 1/49 (2.04%)
Pericardial effusion 4/49 (8.16%)
Right ventricular failure 0/49 (0.00%)
Abdominal pain 1/49 (2.04%)
Ascites 0/49 (0.00%) | Entailment |
Neither the primary trial or the secondary trial require participants to practice yoga. | INTERVENTION 1:
Group I (SparkPeople Program)
Participants receive training on how to use the SparkPeople website, self-monitor their diet using the SparkPeople tool, and to self-monitor their activity daily using the Fitbit monitoring device.
Participants receive weekly motivational reminders to log into the website for 3 months via email, text, or phone, based on patient preference (active phase). Participants then enter the maintenance phase for 3 months without reminders.
Behavioral Dietary Intervention: Use SparkPeople web-based program
Exercise Intervention: Use Fitbit monitor and SparkPeople web-based program
Activity Monitoring Device: Wear Fitbit activity monitoring device
INTERVENTION 2:
Group II (Wait List)
Participants receive the weight loss handout and a Fitbit activity monitor. After 6 months, participants receive the SparkPeople treatment.
Exercise Intervention: Use Fitbit monitor
Activity Monitoring Device: Wear Fitbit activity monitoring device
INTERVENTION 1:
Arm 1: Yoga Intervention
Yoga Intervention
Yoga: Yoga sessions
INTERVENTION 2:
Arm 2: Educational Wellness Group
Educational Wellness Group
Education: Educational Wellness Group | Contradiction |
the primary trial and the secondary trial both evaluate response rates, however the primary trial studies CNS response, whereas the secondary trial studies tumor response, additionally, they test different treatments. | Outcome Measurement:
Central Nervous System (CNS) Objective Response Rate
Outcome Measurement:
Objective Response Rate (ORR) | Entailment |
1 patient in the primary trial suffered from a blood clot blocking their blood vessels. | Adverse Events 1:
Total: 10/31 (32.26%)
Edema, limb 1/31 (3.23%)
Thrombosis1/31 (3.23%)
diarrhea1/31 (3.23%)
Pain 2/31 (6.45%)
Pain, back1/31 (3.23%)
Pain, extrimity limb 1/31 (3.23%)
Syncope 1/31 (3.23%)
Pain, chest/thorax1/31 (3.23%)
hyponatremia 1/31 (3.23%)
fever1/31 (3.23%)
AST 1/31 (3.23%)
infection1/31 (3.23%)
Anorexia 1/31 (3.23%)
Dyspnea 2/31 (6.45%) | Entailment |
There were no cases of Cellulitis, Nausea or Anaemia in the primary trial. | Adverse Events 1:
Total: 8/101 (7.92%)
Vertigo * 1/101 (0.99%)
Infected lymphocele * 1/101 (0.99%)
Ejection fraction decreased * 5/101 (4.95%)
Lymphoedema * 1/101 (0.99%) | Entailment |
Candidates for the primary trial must have adequate renal and hepatic function, and must not be currently receiving amiodarone or have received amiodarone in the 6 months | Inclusion Criteria:
The patient has adequate renal function as shown by the creatinine levels (i.e. within the normal range).
The patient has adequate hepatic function as shown by serum bilirubin levels i.e:
Exclusion Criteria:
The patient is currently receiving amiodarone or has received amiodarone in the 6 months prior to screening. | Entailment |
In the primary trial patient cohort, 3 different types of infections are observed, these are pneumonia, urinary tract and Athlete's foot. | Adverse Events 1:
Total: 14/41 (34.15%)
Cardiac ischemia/infarction 2/41 (4.88%)
Duodenal ulcer 1/41 (2.44%)
Vomiting 2/41 (4.88%)
Fever 2/41 (4.88%)
Death NOS 1/41 (2.44%)
Liver failure 1/41 (2.44%)
Infection - pneumonia 2/41 (4.88%)
Infection - port site 2/41 (4.88%)
Infection - urinary tract 1/41 (2.44%)
Disease progression 3/41 (7.32%)
Confusion 1/41 (2.44%) | Contradiction |
The difference between the two cohorts of the primary trial is that cohort 1 participated in a Hatha yoga, whereas cohort 2 abstained from yoga. | INTERVENTION 1:
Arm I: Yoga Therapy
Patients participated in a Hatha yoga session over 90 minutes twice weekly for 12 weeks. Patients were also encouraged to practice yoga at home. Patients recorded their total home/class practice time in weekly logs.
INTERVENTION 2:
Arm II: Wait-List
Wait-listed women were told to continue performing their usual activities, and to refrain from beginning any yoga practice. After their final assessment they were offered the yoga classes. | Entailment |
the secondary trial and the primary trial both accept patients with progesterone receptors(PgR+) adenocarcinoma of the breast. | Inclusion Criteria:
Histologically confirmed hormone receptor positive (HR+) [(estrogen receptor (ER+) and/or progesterone receptors(PgR+)] breast cancer according to immunohistochemistry (IHC)
Inclusion Criteria:
Patients with histologically confirmed HER-2/neu-overexpressing adenocarcinoma of the breast; this is defined as HER-2+ by immunohistochemistry (IHC) 3+ staining or Fluorescence In-Situ Hybridization (FISH). Prior adjuvant Trastuzumab therapy is permitted. Patients must not be eligible for therapy of known curative potential for metastatic breast cancer if it is identified during the course of the study. | Contradiction |
the secondary trial had a lower total number of patients experiencing adverse events compared to the primary trial. | Adverse Events 1:
Total: 7/37 (18.92%)
Adverse Events 1:
Total: 130/503 (25.84%) | Contradiction |
Every single patient in the primary trial experienced at least 1 adverse event. | Adverse Events 1:
Total: 39/39 (100.00%) | Entailment |
Throughout the primary trial, one patient developed issues with their vision. | Adverse Events 1:
Total: 34/214 (15.89%)
Leukocytosis 0/214 (0.00%)
Atrial fibrillation 0/214 (0.00%)
Cardiac failure congestive 0/214 (0.00%)
Pericardial effusion 1/214 (0.47%)
Cataract 0/214 (0.00%)
Macular fibrosis 0/214 (0.00%)
Constipation 2/214 (0.93%)
Diarrhoea 2/214 (0.93%)
Enterocolitis 0/214 (0.00%)
Ileus 1/214 (0.47%)
Nausea 3/214 (1.40%)
Adverse Events 2:
Total: 27/213 (12.68%)
Leukocytosis 1/213 (0.47%)
Atrial fibrillation 1/213 (0.47%)
Cardiac failure congestive 1/213 (0.47%)
Pericardial effusion 0/213 (0.00%)
Cataract 1/213 (0.47%)
Macular fibrosis 1/213 (0.47%)
Constipation 1/213 (0.47%)
Diarrhoea 1/213 (0.47%)
Enterocolitis 1/213 (0.47%)
Ileus 0/213 (0.00%)
Nausea 0/213 (0.00%) | Entailment |
There were 3 more allergic reactions observed in cohort 1 of the primary trial than cohort 2. | Adverse Events 1:
Total: 5/95 (5.26%)
Febrile neutropenia 0/95 (0.00%)
Neutropenia 0/95 (0.00%)
Atrial fibrillation 0/95 (0.00%)
Pleuropericarditis 0/95 (0.00%)
Vomiting 0/95 (0.00%)
Pryexia 0/95 (0.00%)
Anaphylactic shock 1/95 (1.05%)
Gastroenteritis 0/95 (0.00%)
Fibula fracture 1/95 (1.05%)
Tibia fracture 1/95 (1.05%)
Intervertebral disc protrusion 0/95 (0.00%)
Adverse Events 2:
Total: 3/20 (15.00%)
Febrile neutropenia 0/20 (0.00%)
Neutropenia 0/20 (0.00%)
Atrial fibrillation 1/20 (5.00%)
Pleuropericarditis 1/20 (5.00%)
Vomiting 0/20 (0.00%)
Pryexia 0/20 (0.00%)
Anaphylactic shock 0/20 (0.00%)
Gastroenteritis 1/20 (5.00%)
Fibula fracture 0/20 (0.00%)
Tibia fracture 0/20 (0.00%) | Contradiction |
the primary trial results indicate that CoQ10 reduces the level of fatigue experienced by patients compared to a placebo. | Outcome Measurement:
Effects of Coenzyme Q10 on Fatigue (as Measured by POMS-F) 24 Weeks Following Randomization
POMS-F is the Profile of Mood States - fatigue scale. It ranges from 0 to 28; higher values indicate greater fatigue.
Time frame: 24 weeks
Results 1:
Arm/Group Title: Arm 1 - CoQ10 & Vitamin E
Arm/Group Description: CoQ10 100mg capsule combined with Vitamin E 100 IU taken orally three times per day.
Overall Number of Participants Analyzed: 122
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale 6.96 (0.71)
Results 2:
Arm/Group Title: Arm 2 - Placebo & Vitamin E
Arm/Group Description: Placebo-Vitamin E 100 mg/day in 3 doses
Overall Number of Participants Analyzed: 114
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale 8.33 (0.79) | Entailment |
filgrastim is the only drug in the primary trial given by subcutaneous injection. | INTERVENTION 1:
Treatment (Neoadjuvant Chemotherapy Before Surgery)
Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery.
sunitinib malate: Given PO
paclitaxel: Given IV
doxorubicin hydrochloride: Given IV
cyclophosphamide: Given PO
filgrastim: Given SC
therapeutic conventional surgery: Undergo surgery
laboratory biomarker analysis: Correlative studies
flow cytometry: Correlative studies | Entailment |
More patients in the secondary trial suffered from oedema in their limbs, compared to patients in the primary trial. | Adverse Events 1:
Total: 8/56 (14.29%)
Platelets * 1/56 (1.79%)
Heart failure * 1/56 (1.79%)
Left ventricular systolic dysfunction * 1/56 (1.79%)
Dehydration * 1/56 (1.79%)
Diarrhea * 1/56 (1.79%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary) * 1/56 (1.79%)
Sodium, serum-low (hyponatremia) * 1/56 (1.79%)
Fracture * 2/56 (3.57%)
Adverse Events 1:
Total: 18/70 (25.71%)
Cardiac arrest 1/70 (1.43%)
Pericardial effusion 1/70 (1.43%)
Ear pain 1/70 (1.43%)
Blurred vision 1/70 (1.43%)
Eye disorders - Other, specify 2/70 (2.86%)
Abdominal Pain 5/70 (7.14%)
Colitis 1/70 (1.43%)
Diarrhea 2/70 (2.86%)
Nausea 2/70 (2.86%)
Death NOS 1/70 (1.43%)
Edema limbs 1/70 (1.43%)
Fatigue 3/70 (4.29%) | Entailment |
In total there were more adverse events in cohort 1 of the primary trial, than in cohort 2. | Adverse Events 1:
Total: 4/26 (15.38%)
Febrile neutropenia * 1/26 (3.85%)
Gastric volvulus * 20/26 (0.00%)
General Malaise * 21/26 (3.85%)
Hospitalisation for intrapleuric chemotherapy and thoracentesis * 21/26 (3.85%)
Acute renal failure * 21/26 (3.85%)
Adverse Events 2:
Total: 1/28 (3.57%)
Febrile neutropenia * 0/28 (0.00%)
Gastric volvulus * 21/28 (3.57%)
General Malaise * 20/28 (0.00%)
Hospitalisation for intrapleuric chemotherapy and thoracentesis * 20/28 (0.00%)
Acute renal failure * 20/28 (0.00%) | Entailment |
Fluorouracil, epirubicin, and cyclophosphamide (FEC) are used in both cohorts of the secondary trial, but not in cohort 1 of the primary trial. | INTERVENTION 1:
FSFI Total Score (Pretest)
Administered to participants prior to starting vaginal testosterone therapy.
INTERVENTION 1:
FEC-75 Then Paclitaxel/Trastuzumab
Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
INTERVENTION 2:
Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies | Entailment |
A patient with Histologically confirmed triple-negative breast cancer, with no known Brain metastases and no prior history of either autoimmune disease or cardiac dysfunction, could be eligible for both the secondary trial and the primary trial. | Inclusion Criteria:
Histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor 2 (HER2)-negative adenocarcinoma of the breast with measurable metastatic or locally advanced disease
History of autoimmune disease
Brain metastases (symptomatic or nonsymptomatic) that have not been treated previously, are progressive, or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms from brain metastases within 30 days prior to first study treatment dose
History of clinically significant cardiac dysfunction
Inclusion Criteria:
Women at any age with early stage breast cancer (stage I-II) and American Society of Anesthesiologists (ASA) score of I-II.
Exclusion Criteria:
Ductal carcinoma in situ (DCIS; stage 0 cancer),
Advanced or distant metastatic stage,
Receiving any neoadjuvant therapy,
History of receiving any antibiotics within prior 3 months,
History of immunodeficiency,
Having a remote infection,
History of reaction to study antibiotics,
Denial of signing the consent form. | Entailment |
At least 1 participant in the primary trial showed signs of poor liver function. | Adverse Events 1:
Hepatic function abnormal * 1/109 (0.92%) | Entailment |
Patients in the primary trial receive at most 200mg of IMGN853 by IV every 3 weeks. | INTERVENTION 1:
Cohort A: Advanced Triple-Negative Breast Cancer (TNBC)
6 mg/kg IMGN853 IV Q3W | Contradiction |
There were 4 different adverse events, for which 0 cases were recorded in cohort 1. | Adverse Events 1:
Total: 30/98 (30.61%)
Coagulopathy 1/98 (1.02%)
Febrile neutropenia 7/98 (7.14%)
Pancytopenia 2/98 (2.04%)
Cardiac failure 0/98 (0.00%)
Cardiac failure congestive 0/98 (0.00%)
Pericardial effusion 0/98 (0.00%)
Appendicitis perforated 1/98 (1.02%)
Colitis 1/98 (1.02%)
Ileus 1/98 (1.02%)
Abdominal pain upper 1/98 (1.02%)
Gastrointestinal haemorrhage 0/98 (0.00%) | Entailment |
Gastrointestinal haemorrhage was more common in patients from cohort 2 of the secondary trial. than cohort 1 of the primary trial . | Adverse Events 1:
Total: 13/83 (15.66%)
Cardiac failure congestive 1/83 (1.20%)
Hypothyroidism 1/83 (1.20%)
Nausea 2/83 (2.41%)
Vomiting 2/83 (2.41%)
Diarrhea 1/83 (1.20%)
Gastrointestinal Haemorrhage 1/83 (1.20%)
Asthenia 1/83 (1.20%)
Hyperbilirubinaemia 1/83 (1.20%)
Anal abscess 1/83 (1.20%)
Dehydration 3/83 (3.61%)
Decreased appetite 1/83 (1.20%)
Adverse Events 2:
Total: 5/10 (50.00%)
Febrile neutropenia 0/10 (0.00%)
Neutropenia 0/10 (0.00%)
Thrombocytopenia 1/10 (10.00%)
Cardiac failure congestive 0/10 (0.00%)
Extrasystoles 0/10 (0.00%)
Nausea 0/10 (0.00%)
Abdominal pain 0/10 (0.00%)
Constipation 0/10 (0.00%)
Gastrointestinal haemorrhage 0/10 (0.00%)
Death - unknown cause 0/10 (0.00%)
Thrombosis in device 0/10 (0.00%) | Contradiction |
Most patients in cohort 1 of the primary trial died of unknown causes. | Adverse Events 1:
Total: 7/26 (26.92%)
Febrile neutropenia 1/26 (3.85%)
Neutropenia 0/26 (0.00%)
Thrombocytopenia 0/26 (0.00%)
Cardiac failure congestive 0/26 (0.00%)
Extrasystoles 0/26 (0.00%)
Nausea 1/26 (3.85%)
Abdominal pain 0/26 (0.00%)
Constipation 0/26 (0.00%)
Gastrointestinal haemorrhage 0/26 (0.00%)
Death - unknown cause 1/26 (3.85%)
Thrombosis in device 0/26 (0.00%) | Contradiction |
Patients with an FEV1 of 80% to 120% are ineligible for the primary trial. | Inclusion Criteria:
Adequate pulmonary function | Contradiction |
prior hormonal treatment(s) in the metastatic or adjuvant setting is not necessary for patients in the primary trial, neither is Adequate organ function or a particular racial or ethnic background. | Inclusion criteria:
DISEASE CHARACTERISTICS:
Scheduled to undergo screening mammogram at one of the Boston Medical Center-affiliated primary care clinics and meets 1 of the following criteria:
Dense breast tissue
At high-risk for breast cancer
PATIENT CHARACTERISTICS:
Has 1 of the following racial or ethnic backgrounds based on the patient's country of birth or the mother and father's country of birth:
Hispanic
Haitian Creole
African American
Caucasian
PRIOR CONCURRENT THERAPY:
None specified
Exclusion criteria:
No history of breast cancer, palpable breast mass, abnormal nipple discharge, or other focal complaints warranting diagnostic mammogram | Contradiction |
T2 N1 M0 adenocarcinoma of the breast are eligible for the primary trial. | DISEASE CHARACTERISTICS:
Histologically proven invasive carcinoma of the breast
No evidence of T4, N2-3, or M1 disease prior to surgery
Node positive or high-risk node negative | Entailment |
Informed consent is obligatory for entry in the primary trial. | Inclusion Criteria:
The subject must provide written informed consent with Health Insurance Portability and Accountability Act (HIPAA) authorization before participating in the study | Entailment |
100% of patients in the primary trial suffered adverse events. | Outcome Measurement:
Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious)
[Not Specified]
Time frame: 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up).
Results 1:
Arm/Group Title: AZD4547 80mg bd Cont + Ex 25mg
Arm/Group Description: 80 mg AZD4547 BD continuous + 25 mg exemestane
Overall Number of Participants Analyzed: 5
Measure Type: Number
Unit of Measure: Participants 5
Results 2:
Arm/Group Title: AZD4547 40mg Cont + Ex 25mg
Arm/Group Description: 40 mg AZD4547 BD continuous + 25 mg exemestane
Overall Number of Participants Analyzed: 5
Measure Type: Number
Unit of Measure: Participants 5 | Entailment |
Patients with tumors overexpressing HER-2 are eligible for the secondary trial, but not for the primary trial. | DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the breast
Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC
Stage IV disease
Inclusion Criteria:
FISH+ HER2 gene amplified breast cancer | Contradiction |
None of the adverse events recorded for the primary trial occurred more than once. | Adverse Events 1:
Total: 21/82 (25.61%)
Neutrophils count decreased 1/82 (1.22%)
Cardiac ischemia/infarction 1/82 (1.22%)
Left ventricular systolic dysfunction 1/82 (1.22%)
Hypertension 1/82 (1.22%)
Supraventricular and nodal arrhythmia 1/82 (1.22%)
Anorexia 1/82 (1.22%)
Gastrointestinal perforation 1/82 (1.22%)
Vomiting 1/82 (1.22%)
Dehydration 1/82 (1.22%)
Diarrhoea 1/82 (1.22%) | Entailment |
the primary trial and the secondary trial both use 21 day cycles for their interventions up to a maximum of 10 and 4 cycles respectively. | INTERVENTION 1:
Intelligent Breast Exam, iBE
Single Arm: Additional breast exam by a FDA approved hand-held intelligent breast exam device and a clinical breast exam during their scheduled breast screening appointment. No return visit required for participation.
intelligent Breast Exam, iBE: A bilateral iBE exam will be performed on the entire breast in addition to a clinical breast exam administered by a trained individual. If the patient is selected to participate in the inter-rater reliability portion of the study, the subject will undergo both the iBE and the clinical breast exams twice sequentially performed by two different separately trained individuals during the same visit.
INTERVENTION 1:
Phase 1: Addition of Supine MRI to Conventional Imaging
Pre-operative supine MRI with intraoperative optical scanning and tracking (group MRI) | Contradiction |
All patients in the primary trial had to drink 4 cups of water, either Alkaline Water or Distilled, depending on which cohort they are in. | INTERVENTION 1:
Arm I: Alkaline Water
Patients undergo external beam radiation therapy QD, 5 days a week for 6 weeks. Patients drink 8 ounces of alkaline water within 30 minutes immediately prior to and after undergoing radiation therapy.
alkaline water: Patients drink 8 ounces of alkaline water within 30 minutes immediately prior to and after undergoing radiation therapy.
external beam radiation therapy (EBRT): Patients undergo external beam radiation therapy QD, 5 days a week for 6 weeks.
INTERVENTION 2:
Arm II: Distilled Water
Patients undergo external beam radiation therapy as in arm I. Patients also drink 8 ounces of distilled water within 30 minutes immediately prior to and after undergoing radiation therapy
distilled water: Patients also drink 8 ounces of distilled water within 30 minutes immediately prior to and after undergoing radiation therapy.
external beam radiation therapy (EBRT): Patients undergo external beam radiation therapy QD, 5 days a week for 6 weeks. | Contradiction |
Cohort 1 of the primary trial had more cases of urinary infections and lumbar fractures than cohort 2. | Adverse Events 1:
Urinary tract infection 1/26 (3.85%)
Lumbar vertebral fracture 1/26 (3.85%)
Adverse Events 2:
Urinary tract infection 0/13 (0.00%)
Lumbar vertebral fracture 0/13 (0.00%) | Entailment |
A higher percent of patients in cohort 1 of the secondary trial experienced stomatitis, than in cohort 1 of the primary trial. | Adverse Events 1:
Total: 13/72 (18.06%)
Adverse Events 1:
Total: 52/133 (39.10%) | Contradiction |
The the primary trial placebo group had a better mean retention than the donepezil hydrochloride PO QD group. | Outcome Measurement:
Retention
Retention is the percentage of participants who stay in the study for 24 weeks.
Time frame: 24 Weeks
Results 1:
Arm/Group Title: Arm I
Arm/Group Description: Patients receive donepezil hydrochloride PO QD.
donepezil hydrochloride: Given PO
Overall Number of Participants Analyzed: 31
Mean (Standard Error)
Unit of Measure: percentage of participants 71.0 (8.3)
Results 2:
Arm/Group Title: Arm II
Arm/Group Description: Patients receive placebo PO QD.
Placebo: Given PO
Overall Number of Participants Analyzed: 31
Mean (Standard Error)
Unit of Measure: percentage of participants 80.7 (7.2) | Entailment |
Patients with a nonpalpable breast lesion and 0 palpable axillary lymph nodes are eligible for the primary trial. | Palpable or nonpalpable breast lesion
No palpable axillary lymph node(s) | Entailment |
Participants in the primary trial are assigned an intervention depending on their HIV diagnosis, whereas in the secondary trial the interventions are randomly assigned. | INTERVENTION 1:
Healthy Volunteers
Healthy women will be screened for Magnetic Resonance Imaging (MRI) contraindications, and then undergo contrast injection, and SWIFT acquisition.
Magnetic resonance imaging: Patients and healthy volunteers will be first screened for MRI contraindications. The SWIFT MRI workflow will be performed as follows:
INTERVENTION 2:
Breast Cancer Patients
Breast cancer patients who have suspected breast lesion that will be biopsied will be screened for Magnetic Resonance Imaging (MRI) contraindications, and then undergo contrast injection and SWIFT acquisition.
Magnetic resonance imaging: Patients and healthy volunteers will be first screened for MRI contraindications. The SWIFT MRI workflow will be performed as follows:
INTERVENTION 1:
Hydrophor (Group A)
Group A (current standard of care): Patients will be instructed (by nurses and with printed study materials) to apply a thin layer of the Hydrophor daily, starting at the onset of radiation therapy (RT) and continuing until 2 weeks after the final RT session or until the RT site is healed (whichever is first). Hydrophor application should include the entire treatment area, including the axillae and shoulder/back area in patients treated with modified radical mastectomy. To avoid possible build-up effects, patients should not apply the Hydrophor within 4 hours of receiving RT. Patients should wash the application area daily with perfume-free soap and tap water. Patients will be asked to refrain from using other topical agents in the irradiated area.
INTERVENTION 2:
MediHoney (Group B)
Group B (study target): Patients will be instructed (by nurses and with printed study materials) to apply a thin layer of the Medihoney daily, starting at the onset of RT and continuing until 2 weeks after the final RT session or until the RT site is healed (whichever is first). Medihoney application should include the entire treatment area, including the axillae and shoulder/back area in patients treated with modified radical mastectomy. To avoid possible build-up effects, patients should not apply the Medihoney within 4 hours of receiving RT. Patients should wash the application area daily with perfume-free soap and tap water. Patients will be asked to refrain from using other topical agents in the irradiated area. | Contradiction |
Patients in the primary trial and the secondary trial did not have any of the same adverse events. | Adverse Events 1:
Total: 6/25 (24.00%)
Supraventricular extrasystoles 1/25 (4.00%)
Ventricular extrasystoles 1/25 (4.00%)
Ascites 2/25 (8.00%)
Diarrhea 1/25 (4.00%)
Nausea 1/25 (4.00%)
Pancreatitis 1/25 (4.00%)
Small intestinal obstruction 1/25 (4.00%)
Vomiting 1/25 (4.00%)
Bile duct obstruction 1/25 (4.00%)
Portal hypertension 1/25 (4.00%)
Adverse Events 1:
Total: 6/19 (31.58%)
Febrile neutropenia [1]1/19 (5.26%)
Fatigue [1]1/19 (5.26%)
Pyrexia [1]1/19 (5.26%)
Fracture [1]1/19 (5.26%)
Hip Fracture [1]1/19 (5.26%)
Headache [2]1/19 (5.26%) | Entailment |
Only one adverse event is observed in patients from cohort 1 of the primary trial. | Adverse Events 1:
Total: 1/25 (4.00%)
Diarrhoea 0/25 (0.00%)
Breast abscess 0/25 (0.00%)
Breast cellulitis 0/25 (0.00%)
Syncope 1/25 (4.00%) | Entailment |
All of the adverse event cases in the primary trial occurred in patients from cohort 2. | Adverse Events 1:
Total: 0/77 (0.00%)
Neutropenia [1]0/77 (0.00%)
Left ventricular dysfunction 0/77 (0.00%)
Cardiac ischemia 0/77 (0.00%)
Gastrointestinal pain 0/77 (0.00%)
Colitis 0/77 (0.00%)
Febrile neutropenia 0/77 (0.00%)
Pulmonary/upper respiratory infection 0/77 (0.00%)
Diverticulitis 0/77 (0.00%)
Motor neuropathy 0/77 (0.00%)
Endometrial mucosa thinkening 0/77 (0.00%)
Adverse Events 2:
Total: 12/85 (14.12%)
Neutropenia [1]1/85 (1.18%)
Left ventricular dysfunction 1/85 (1.18%)
Cardiac ischemia 2/85 (2.35%)
Gastrointestinal pain 1/85 (1.18%)
Colitis 1/85 (1.18%)
Febrile neutropenia 3/85 (3.53%)
Pulmonary/upper respiratory infection 1/85 (1.18%)
Diverticulitis 1/85 (1.18%)
Motor neuropathy 1/85 (1.18%)
Endometrial mucosa thinkening 1/85 (1.18%) | Entailment |
In the primary trial Low Dose Magnesium Oxide is 5% less than high dose Magnesium Oxide. | INTERVENTION 1:
Low Dose Magnesium Oxide (800 mg/Day)
Week 2:
Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Week 3:
Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Weeks 4-9:
Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
INTERVENTION 2:
High Dose Magnesium Oxide (1200 mg/Day)
Week 2:
Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Week 3:
Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).
Weeks 4-9:
Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD). | Contradiction |
All of the adverse events recorded in the primary trial occurred in patients from cohort 1. | Adverse Events 1:
Total: 5/45 (11.11%)
Neutrophils/granulocytes (ANC/AGC) * [1]0/45 (0.00%)
Neutrophils/granulocytes (ANC/AGC) * [2]0/45 (0.00%)
Diabetes decompensation * 0/45 (0.00%)
Diarrhea * [2]0/45 (0.00%)
Mucositis/stomatitis and Vomiting * [3]0/45 (0.00%)
Pancreatitis * [4]1/45 (2.22%)
Febrile neutropenia * [2]3/45 (6.67%)
Adverse Events 2:
Total: 0/46 (0.00%)
Neutrophils/granulocytes (ANC/AGC) * [1]0/46 (0.00%)
Neutrophils/granulocytes (ANC/AGC) * [2]0/46 (0.00%)
Diabetes decompensation * 0/46 (0.00%)
Diarrhea * [2]0/46 (0.00%)
Mucositis/stomatitis and Vomiting * [3]0/46 (0.00%)
Pancreatitis * [4]0/46 (0.00%)
Febrile neutropenia * [2]0/46 (0.00%)
Infection pulmonary/ Upper airway NOS * [5]0/46 (0.00%) | Entailment |
the primary trial only has one test cohort whereas the secondary trial has both a test and control group. | INTERVENTION 1:
Phase 1: Addition of Supine MRI to Conventional Imaging
Pre-operative supine MRI with intraoperative optical scanning and tracking (group MRI)
INTERVENTION 1:
Decision Support Workshop
The decision support workshop will be 2 hours in duration on the morning of the consultation and will be facilitated by a dedicated social worker from psycho-oncology.
Decision Support Workshop: Incorporates the key components of shared decision-making and decision support with the philosophy of delivering supportive care to cancer patients.
Surgeon (30 mins): treatment options for breast reconstruction with indications/ contraindications, advantages / disadvantages, expected post-operative course, aesthetic result and complications with probabilities
Registered nurse (30 mins): preparing for surgery, postoperative recovery and how to navigate the health care system
Social worker (30 mins): values clarification exercise
Breast reconstruction patient volunteer (30 mins) questions and answers about her personal experience
INTERVENTION 2:
Standard Care
Routine pre-consultation education | Entailment |
the primary trial records instances of Rectal Hemorrhage within its patient cohort, whereas the secondary trial records Vaginal hemorrhages. | Adverse Events 1:
Total: 8/44 (18.18%)
Febrile neutropenia4/44 (9.09%)
Rectal bleeding1/44 (2.27%)
Chest pain2/44 (4.55%)
Fever1/44 (2.27%)
Catheter site infection1/44 (2.27%)
Neutrophil count decreased1/44 (2.27%)
Dizziness1/44 (2.27%)
Adverse Events 1:
Total: 331/1634 (20.26%)
Anemia 3/1634 (0.18%)
Coagulation disorders 1/1634 (0.06%)
Hemorrhage Vaginal 1/1634 (0.06%)
Leukopenia 18/1634 (1.10%)
Lymphadenopathy 0/1634 (0.00%)
Lymphedema 0/1634 (0.00%)
Pancytopenia 0/1634 (0.00%)
Thrombocytopenia 0/1634 (0.00%)
Arrhythmia 3/1634 (0.18%)
Arrhythmia Ventricular 0/1634 (0.00%)
Cardiomyopathy 1/1634 (0.06%) | Entailment |
HIV+ Patients are excluded from both the secondary trial and the primary trial. | Exclusion Criteria:
Evidence of HIV infection
Exclusion Criteria:
HIV positive patients | Entailment |
To be eligible for both the secondary trial and the primary trial patients must satisfy all the following conditions; alkaline phosphatase < 2 x ULN, aspartate aminotransferase <= 1.5 x ULN and Hemoglobin > 10 g/dL. | The following criteria for evidence of adequate hepatic function must be met:
alkaline phosphatase must be less than 2.5 x ULN for the lab; and
aspartate aminotransferase (AST) must be less than/equal to 1.5 x ULN for the lab.
Platelet count must be greater than/equal to 100,000/mm^3.
Hemoglobin must be greater than/equal to 10 g/dL.
Platelets > 100,000/mm^3
Hemoglobin > 10 g/dL
AST < 2 times upper limit of normal (ULN)
Alkaline phosphatase < 2 times ULN | Entailment |
Patients in cohort 1 of the primary trial may receive gradually increasing doses of Afatinib monotherapy from 40mg PO to 50mg PO. | INTERVENTION 1:
Afatinib Mono
Afatinib monotherapy administered orally: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Entailment |
The Trastuzumab arm of the primary trial reported a pCR rate of 54%, significantly worse results than the Lapatinib arm which achieved a pCR rate of 45%. | Outcome Measurement:
Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy
A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.
Time frame: Week 26
Results 1:
Arm/Group Title: Trastuzumab
Arm/Group Description: Participants received trastuzumab alone (a loading dose of 4 milligrams [mg]/kilogram [kg] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil [5-FU] 500 mg/meters squared [m^2], epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.
Overall Number of Participants Analyzed: 26
Measure Type: Number
Unit of Measure: percentage of participants 54.0
Results 2:
Arm/Group Title: Lapatinib
Arm/Group Description: Participants received lapatinib alone (1250 mg orally [PO] once daily [QD]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m^2, epirubicin 75 mg/m^2, cyclophosphamide 500 mg/m^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.
Overall Number of Participants Analyzed: 29
Measure Type: Number
Unit of Measure: percentage of participants 45.0 | Contradiction |
the primary trial and the secondary trial do not use chemotherapy, radiotherapy or mammography in their interventions | INTERVENTION 1:
Digital Breast Tomosynthesis
Digital Breast Tomosynthesis + Synthetic Mammography (DBT)
The DBT was independently read by two radiologists. A consensus meeting decided whether to recall the woman or not.
Women selected for further assessment (positive screening exam) was recalled.
Digital Breast Tomosynthesis + Synthetic Mammography: Two-view tomosynthesis performed with GE SenoClaire 3D Breast Tomosynthesis.
INTERVENTION 2:
Digital Mammography
The digital mammograms was independently read by two radiologists. A consensus meeting decided whether to recall the woman or not.
Women selected for further assessment (positive screening exam) was recalled.
Digital mammography: Two-view digital mammography performed with GE SenoClaire 3D Breast Tomosynthesis.
INTERVENTION 1:
Arm I: Yoga Therapy
Patients participated in a Hatha yoga session over 90 minutes twice weekly for 12 weeks. Patients were also encouraged to practice yoga at home. Patients recorded their total home/class practice time in weekly logs.
INTERVENTION 2:
Arm II: Wait-List
Wait-listed women were told to continue performing their usual activities, and to refrain from beginning any yoga practice. After their final assessment they were offered the yoga classes. | Contradiction |
Patients with aromatase inhibitor associated musculoskeletal symptoms, such as Grade 1 or above musculoskeletal pain or sensory neuropathy, are eligible for the primary trial. | Inclusion Criteria:
AI-associated musculoskeletal symptoms, defined as:
Grade 1 or higher musculoskeletal pain that developed or worsened (6 or 7 on CGICS) during AI therapy or
Grade 1 or higher sensory neuropathy that developed or worsened (6 or 7 on CGICS) during AI therapy; | Entailment |
Radiotherapy is used in all cohorts of the primary trial and the secondary trial. | INTERVENTION 1:
Radiotherapy/Supportive Care (A)
Patients receive radiotherapy and healing touch therapy from a healing-touch therapist once a week for the duration of their radiotherapy
INTERVENTION 2:
Control ARM (B)
Patients receive radiotherapy and sham healing touch therapy from a sham healing-touch therapist once a week for the duration of their radiotherapy
INTERVENTION 1:
Participants With Stage 0-III Breast Cancer
Women with Stage 0-III breast cancer, treated with breast conserving surgery or mastectomy and clear margins, will receive 15 doses of radiation over three weeks.
Hypofractionated Simultaneous Integrated Boost Radiotherapy: Participants will receive radiotherapy treatments to the whole breast or chest wall to a dose of 2.66 Gy per day x 15 fractions simultaneously with a boost treatment. The boost treatment will be given on the same days as the whole breast treatment. The lumpectomy cavity + scar (in lumpectomy patients) or chest wall scar (mastectomy patients) will receive 0.54 Gy per day x 15 fractions. | Entailment |
There was 1 MRSA infection in cohort 1 of the secondary trial and 4 in cohort 2 of the primary trial. | Adverse Events 1:
Total: 51/486 (10.49%)
ANEMIA 1/486 (0.21%)
NEUTROPENIA 4/486 (0.82%)
FIBRILLATION ATRIAL 1/486 (0.21%)
ABDOMINAL PAIN 2/486 (0.41%)
BLOATING 1/486 (0.21%)
BOWEL PERFORATION 1/486 (0.21%)
COLITIS 1/486 (0.21%)
DEHYDRATION 5/486 (1.03%)
DIARRHEA 5/486 (1.03%)
GASTRIC INFLAMMATION 1/486 (0.21%)
NAUSEA 3/486 (0.62%)
NAUSEA AND VOMITING 1/486 (0.21%)
Adverse Events 1:
Total: 17/40 (42.50%)
Anaemia 2/40 (5.00%)
Febrile Neutropenia 3/40 (7.50%)
Neutropenia 2/40 (5.00%)
Thrombocytopenia 5/40 (12.50%)
Pericardial Effusion 1/40 (2.50%)
Abdominal Pain Lower 1/40 (2.50%)
Disease Progression 6/40 (15.00%)
Fatigue 1/40 (2.50%)
Pyrexia 3/40 (7.50%)
Septic Shock 1/40 (2.50%)
Streptococcal Infection 1/40 (2.50%) | Contradiction |
the primary trial's intervention section does not describe the intervention dosage, frequency or duration. | INTERVENTION 1:
Recruitment Population
Pre-randomization recruitment and enrollment | Entailment |
Over 9 patients in the primary trial suffered from adverse events associated with a low number of white blood cells present in the bloodstream. | Adverse Events 1:
Febrile Neutropenia * 5/67 (7.46%) | Contradiction |
Each patient in the primary trial receives 3 different drugs, whereas in the secondary trial patients are given supportive-expressive group psychotherapy instead. | INTERVENTION 1:
Pertuzumab + Trastuzumab + Taxane
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
INTERVENTION 1:
Afatinib 50 mg
Patients received continuous daily dosing with Afatinib 50 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial.
INTERVENTION 2:
Lapatinib 1500 mg
Patients received continuous daily dosing with Lapatinib 1500 mg orally from Day 1 to Day 21 of each treatment course. 2 treatment courses were to be given in the trial. | Contradiction |
On average patients from both arms of the primary trial experienced Grade 4 Neutropenia for the same amount of time. | Outcome Measurement:
Duration in Days of Grade 4 Neutropenia in Chemotherapy Cycle 1
Eligible subjects were randomized in a 1:1 ratio. Subjects were dosed with either the F 627 20 mg/dose PFS or Neulasta® 6 mg/dose as the study drug in each chemotherapy cycle. Subjects remained in their assigned treatment arm throughout the study. Subjects were dosed subcutaneously (SC) 24 to 28 hours after receiving TC chemotherapy (75 mg/m2 docetaxel + 600 mg/m2 cyclophosphamide) on Day 2 of each chemotherapy cycle that the subject underwent (up to 4 cycles). Grade 4 (severe) neutropenia was defined as ANC <0.5 × 109/L within the first 12 days of chemotherapy.
Time frame: The first of 4, 21-day chemotherapy cycles (average 3 weeks)
Results 1:
Arm/Group Title: F-627
Arm/Group Description: F-627, 20 mg fixed dose pre-filled syringe, administered on Day 2 of each of 4 chemotherapy cycles.
F-627: single dose pre-filled syringe
Overall Number of Participants Analyzed: 197
Mean (Standard Deviation)
Unit of Measure: days 0.2 (0.51)
Results 2:
Arm/Group Title: Neulasta
Arm/Group Description: 6 mg fixed dose Neulasta , administered on Day 2 of each of 4 chemotherapy cycles
Neulasta: single dose pre-filled syringe
Overall Number of Participants Analyzed: 196
Mean (Standard Deviation)
Unit of Measure: days 0.2 (0.45) | Entailment |
In cohort 2 and 3 of the primary trial there was only case 1 of jaundice. | Adverse Events 1:
Total: 17/65 (26.15%)
Febrile neutropenia 3/65 (4.62%)
Neutropenia 2/65 (3.08%)
Pancytopenia 1/65 (1.54%)
Thrombocytopenia 1/65 (1.54%)
Cardiac arrest 2/65 (3.08%)
Myocardial infarction 1/65 (1.54%)
Diarrhoea 5/65 (7.69%)
Stomatitis 1/65 (1.54%)
Vomiting 2/65 (3.08%)
Fatigue 1/65 (1.54%)
Jaundice 1/65 (1.54%)
Neutropenic infection 2/65 (3.08%) | Contradiction |
the primary trial and the secondary trial have entirely different adverse event reports. | Adverse Events 1:
Total: 2/17 (11.76%)
Nausea * 1/17 (5.88%)
Pain - Abdomen NOS * 1/17 (5.88%)
Constipation * 1/17 (5.88%)
Adverse Events 1:
Total: 19/51 (37.25%)
Febrile neutropenia 6/51 (11.76%)
Anaemia 1/51 (1.96%)
Leukopenia 1/51 (1.96%)
Neutropenia 1/51 (1.96%)
Thrombocytopenia 0/51 (0.00%)
Pericarditis 1/51 (1.96%)
Atrial flutter 0/51 (0.00%)
Cardiac failure congestive 0/51 (0.00%)
Visual impairment 0/51 (0.00%)
Dysphagia 1/51 (1.96%)
Abdominal pain 0/51 (0.00%)
Chills 1/51 (1.96%)
Adverse Events 2:
Total: 17/50 (34.00%)
Febrile neutropenia 0/50 (0.00%)
Anaemia 1/50 (2.00%)
Leukopenia 0/50 (0.00%)
Neutropenia 1/50 (2.00%)
Thrombocytopenia 1/50 (2.00%)
Pericarditis 0/50 (0.00%)
Atrial flutter 1/50 (2.00%)
Cardiac failure congestive 1/50 (2.00%)
Visual impairment 1/50 (2.00%)
Dysphagia 0/50 (0.00%)
Abdominal pain 1/50 (2.00%)
Chills 0/50 (0.00%) | Entailment |
the primary trial had a total of 3 patients experiencing Pancreatic Cancer, the secondary trial had 0. | Adverse Events 1:
Total: 103/1408 (7.32%)
Anaemia 1/1408 (0.07%)
Angina pectoris 1/1408 (0.07%)
Myocardial infarction 1/1408 (0.07%)
Atrial fibrillation 0/1408 (0.00%)
Sinus tachycardia 0/1408 (0.00%)
Tachycardia 0/1408 (0.00%)
Vertigo 0/1408 (0.00%)
Diarrhoea 22/1408 (1.56%)
Vomiting 12/1408 (0.85%)
Nausea 4/1408 (0.28%)
Abdominal pain 2/1408 (0.14%)
Pancreatitis 2/1408 (0.14%)
Adverse Events 2:
Total: 85/1408 (6.04%)
Anaemia 1/1408 (0.07%)
Angina pectoris 0/1408 (0.00%)
Myocardial infarction 1/1408 (0.07%)
Atrial fibrillation 1/1408 (0.07%)
Sinus tachycardia 1/1408 (0.07%)
Tachycardia 1/1408 (0.07%)
Vertigo 1/1408 (0.07%)
Diarrhoea 1/1408 (0.07%)
Vomiting 1/1408 (0.07%)
Nausea 1/1408 (0.07%)
Abdominal pain 0/1408 (0.00%)
Pancreatitis 1/1408 (0.07%)
Adverse Events 1:
Total: 46/170 (27.06%)
Anaemia 1/170 (0.59%)
Febrile neutropenia 1/170 (0.59%)
Cardiac tamponade 1/170 (0.59%)
Myocarditis 1/170 (0.59%)
Pericardial effusion 2/170 (1.18%)
Pericarditis 1/170 (0.59%)
Colitis 1/170 (0.59%)
Constipation 1/170 (0.59%)
Diarrhoea 0/170 (0.00%)
Gastroenteritis eosinophilic 0/170 (0.00%)
Intestinal obstruction 0/170 (0.00%)
Adverse Events 2:
Total: 0/1 (0.00%)
Anaemia 0/1 (0.00%)
Febrile neutropenia 0/1 (0.00%)
Cardiac tamponade 0/1 (0.00%)
Myocarditis 0/1 (0.00%)
Pericardial effusion 0/1 (0.00%)
Pericarditis 0/1 (0.00%)
Colitis 0/1 (0.00%)
Constipation 0/1 (0.00%)
Diarrhoea 0/1 (0.00%)
Gastroenteritis eosinophilic 0/1 (0.00%)
Intestinal obstruction 0/1 (0.00%)
Nausea 0/1 (0.00%) | Contradiction |
Every participant in the secondary trial and the primary trial undergoes Laboratory Biomarker Analysis. | INTERVENTION 1:
Arm I (Omega-3 Fatty Acid)
Patients receive omega-3 fatty acid PO daily for 7-14 days.
omega-3 fatty acid: Given PO
laboratory biomarker analysis: Correlative studies
INTERVENTION 2:
Arm II (Placebo)
Patients receive placebo PO daily for 7-14 days.
placebo: Given PO
laboratory biomarker analysis: Correlative studies
INTERVENTION 1:
Arm I (Curcumin-based Gel)
Patients apply curcumin-based gel topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Curcumin-based Gel: Applied topically
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
INTERVENTION 2:
Arm II (HPR Plus)
Patients apply HPR Plus™ topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Dermatologic Complications Management: Apply HPR Plus topically
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies | Entailment |
Potential participants will be considered regardless of the hormone receptivity of their breast cancer. | Will not exclude participants based on hormone receptivity, one exception is that we will exclude HER2 positive BCS | Contradiction |
patients with Karnofsky Index = 72 are eligible for the primary trial. | Inclusion Criteria :
women with primary breast cancer, without ongoing support for substance use.
An AUDIT-C score >1 or more than one cigarette smoked per day.
Individuals able to consent to benefit of intervention focused on substance use. (Karnofsky Index >70). | Entailment |
the primary trial uses different inclusion criteria for its cohorts, the secondary trial only uses one set on inclusion criteria for all cohorts. | Inclusion Criteria:
(Cohort 1) Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) is allowed if distant metastases have been non-progressing (stable or responding) on that regimen for > or = 12 weeks and skin metastases are non-responsive (stable or progressing) as assessed by the investigator.
(Cohort 2) Any concurrent systemic therapy is allowed
Inclusion Criteria:
Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
HER2+ status defined as IHC 3+ staining or in situ hybridization positive
Patients with resistance to trastuzumab
Prior taxane therapy
Patients with an ECOG performance status of 0 - 2
Patients with measurable disease as per RECIST criteria
Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
Patients must meet laboratory criteria defined in the study within 21 days prior to randomization
Exclusion Criteria:
Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
More than three prior chemotherapy lines for advanced disease.
Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
Peripheral neuropathy grade 2 at randomization
Active cardiac disease
History of cardiac dysfunction
Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
Known hypersensitivity to any study medication
Breastfeeding or pregnant | Entailment |
the primary trial and the secondary trial only recorded one type of acute adverse event. | Adverse Events 1:
Total: 23/78 (29.49%)
Febrile neutropenia * 4/78 (5.13%)
Neutropenia * 1/78 (1.28%)
Thrombocytopenia * 0/78 (0.00%)
Acute coronary syndrome * 1/78 (1.28%)
Cardiac failure congestive * 1/78 (1.28%)
Myocardial infarction * 1/78 (1.28%)
Cardiomyopathy * 0/78 (0.00%)
Abdominal pain * 1/78 (1.28%)
Diarrhoea * 1/78 (1.28%)
Upper gastrointestinal haemorrhage * 1/78 (1.28%)
Adverse Events 1:
Total: 29/30 (96.67%)
Febrile neutropenia [1]3/30 (10.00%)
Lymphatics 1/30 (3.33%)
Diarrhea (without colostomy) 5/30 (16.67%)
Abdominal pain or cramping 2/30 (6.67%)
Colitis 1/30 (3.33%)
Dehydration 1/30 (3.33%)
Nausea 1/30 (3.33%)
Stomatitis/pharyngitis (oral/pharyngeal/mucositis) 1/30 (3.33%)
Vomiting 1/30 (3.33%) | Contradiction |
The Ridaforolimus + Dalotuzumab + Exemestane group of the primary trial had a median PFS of over 5 months. | Outcome Measurement:
1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
Time frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
Results 1:
Arm/Group Title: Ridaforolimus + Dalotuzumab + Exemestane
Arm/Group Description: Participants received ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed: 40
Median (95% Confidence Interval)
Unit of Measure: Weeks 23.29 (8.71 to 38.43) | Entailment |
1 patient in the primary trial died in an event not associated with a specifc CTCAE term. | Adverse Events 1:
Total: 18/70 (25.71%)
Cardiac arrest 1/70 (1.43%)
Pericardial effusion 1/70 (1.43%)
Ear pain 1/70 (1.43%)
Blurred vision 1/70 (1.43%)
Eye disorders - Other, specify 2/70 (2.86%)
Abdominal Pain 5/70 (7.14%)
Colitis 1/70 (1.43%)
Diarrhea 2/70 (2.86%)
Nausea 2/70 (2.86%)
Death NOS 1/70 (1.43%)
Edema limbs 1/70 (1.43%)
Fatigue 3/70 (4.29%) | Entailment |
The majority of patients in the primary trial and the secondary trial experienced an adverse event. | Adverse Events 1:
Total: 24/32 (75.00%)
Adverse Events 1:
Total: 30/112 (26.79%)
Thrombocytopenia 1/112 (0.89%)
Dysphagia 1/112 (0.89%)
Haemorrhoidal haemorrhage 1/112 (0.89%)
Oesophageal stenosis 1/112 (0.89%)
Upper gastrointestinal haemorrhage 1/112 (0.89%)
Asthenia 1/112 (0.89%)
Disease progression 1/112 (0.89%)
Hepatotoxicity 1/112 (0.89%)
Cellulitis 3/112 (2.68%)
Pneumonia 2/112 (1.79%)
Osteomyelitis 1/112 (0.89%) | Contradiction |
Patients with measurable diseases are only eligible for phase 2 of the primary trial. | Measurable or non-measurable disease for phase I study (The Phase I portion of this study closed and the Phase II portion of the study opened as per NCCTG Addendum 6, effective January 23, 2012.)
Measurable disease only for phase II study | Contradiction |
There was no adverse event in cohort 2 of the primary trial which occurred in more than 5% of patients. | Adverse Events 2:
Anaemia 3/202 (1.49%)
Febrile neutropenia 2/202 (0.99%)
Leukocytosis 0/202 (0.00%)
Leukopenia 0/202 (0.00%)
Neutropenia 0/202 (0.00%)
Pancytopenia 1/202 (0.50%)
Atrial fibrillation 1/202 (0.50%)
Cardiac failure congestive 1/202 (0.50%)
Palpitations 1/202 (0.50%)
Pericardial effusion 1/202 (0.50%)
Supraventricular tachycardia 1/202 (0.50%) | Entailment |
Presence of Extracranial metastases is part of the exclusion critera for the primary trial. | DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed breast cancer with radiographically confirmed metastases to the brain
Extracranial metastases allowed | Contradiction |
Lower doses of MM-121 and Paclitaxel are utilised in cohort1 of the primary trial than in cohort 2. | INTERVENTION 1:
Part 1: Dose Escalation: Cohort 1
MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV
INTERVENTION 2:
Part 1: Dose Escalation: Cohort 2
MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV
Paclitaxel - 80mg/m2 weekly IV | Contradiction |
A female with Hemoglobin > 10.0 g/dl, Absolute neutrophil count 1,733/mm3, platelet count = 100,000/µl and total bilirubin > 1.6 x ULN are eligilbe for the primary trial. | Hemoglobin > 9.0 g/dl
Absolute neutrophil count (ANC) > 1,500/mm3
Platelet count = 100,000/µl
Total bilirubin =1.5 x the upper limit of normal. | Entailment |
Subsets and Splits