A Randomized Phase II, Double Blind Trial of Standard Chemotherapy With Metformin (vs Placebo) in Women With Metastatic Breast Cancer Receiving First, Second, Third or Fourth Line Chemotherapy With Anthracycline, Taxane, Platinum, Capecitabine or Vinorelbine Based Regimens
A Trial of Standard Chemotherapy With Metformin (vs Placebo) in Women With Metastatic Breast Cancer
Sponsors
Source
Ozmosis Research Inc.
Oversight Info
Has Dmc
Yes
Brief Summary
The purpose of this study is to determine if the addition of metformin to standard
chemotherapy improves progression free survival in women with metastatic breast cancer.
Overall Status
Completed
Start Date
2011-08-22
Completion Date
2018-03-26
Primary Completion Date
2016-07-14
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Progression free survival. |
From date of randomization to first documented progression or death, which ever occurs first, assessed up to 3 years. |
Secondary Outcome
Measure |
Time Frame |
Overall response rate |
From baseline until time of best response, assessed up to 3 years |
To examine the effect of the addition of metformin to standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine) on change in frequency and severity of adverse events. |
up to 3 years |
Quality of life and treatment related symptoms |
up to 3 years |
Physiological parameters fasting insulin, glucose and HOMA change, and to explore the association of these changes with progression free survival (in all subjects) and tumor response (in subjects with measurable disease). |
Up to 3 years |
Immunohistochemical predictors of metformin benefit and to explore changes in these variables in women who undergo serial biopsies of their metastases. |
Baseline and 3 weeks. |
Gene expression predictors of potential metformin benefit including exploration of changes in these variables in women who undergo serial biopsies of their metastases |
Baseline and 4 weeks |
Enrollment
40
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
metformin 850 mg bid in addition to standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).
Number of cycles: Until progression or unacceptable toxicity develops.
Arm Group Label
Metformin
Intervention Type
Drug
Intervention Name
Description
Placebo bid in addition to standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).
Number of cycles: until progression or unacceptable toxicity develops.
Arm Group Label
Placebo
Eligibility
Criteria
Inclusion Criteria:
- Histologically proven invasive breast cancer with metastatic spread outside of breast,
ipsilateral axillary and supraclavicular nodal areas (Histological confirmation of
metastases is not required) OR, Locally advanced breast cancer that is refractory to
initial anticancer treatment.
- A decision has been made to administer single or multiple agent first or second line
chemotherapy that includes one of the following agents: anthracycline, taxane,
platinum, capecitabine.
- Age: 18 to 75 years at the time of registration
- Invasive breast cancer, any ER or PgR status
- ECOG performance status 0-2
- Life expectancy of at least 6 months
- Adequate hepatic and renal function (SGOT and ALT < 1.8 X upper limit of normal for
the institution, alkaline phosphatase ≤ 2X upper limit of normal for the institution,
bilirubin within normal limits for the institution (expect in patients with Gilbert's
syndrome who will be eligible regardless of bilirubin) and creatinine ≤ 130 umol/L)
- Blood counts: Neutrophils must be at least 1,000/mm3 and Platelets ≥ 75,000/mm3.
- Ability to understand and to provide written informed consent for the study
- Absence of any psychological, familial, sociological, or other patient related factors
that might preclude compliance with the study protocol
- Measurable or non measurable (but evaluable) tumour must be present - radiologic or
clinical evaluation must have been performed within 4 weeks prior to registration.
Exclusion Criteria:
- More than one previous line(s) of chemotherapy for metastatic disease - if prior
chemotherapy has been administered, the last date of treatment must have been given at
least 3 weeks prior to registration [any adjuvant systemic treatment is acceptable]
- If prior hormone therapy (as adjuvant or metastatic therapy) has been administered, it
must have been stopped at least 3 weeks prior to registration
- Radiotherapy to a target or non target lesion within 4 weeks of registration
- Known CNS metastases
- History of cardiac failure
- Known hypersensitivity or allergy to metformin
- History of or known diabetes or baseline fasting glucose ≥ 7.0 mmol/L
- History of lactic or other metabolic acidosis
- Use of metformin within 3 months of registration
- Current or planned pregnancy or lactation in women of child-bearing potential.
Patients of childbearing potential must have a negative serum pregnancy test.
- Fertile patients must agree to use an effective method of contraception while on study
treatment; which could include IUD, condoms or other barrier methods of birth control
- Habitual alcohol intake of more than three drinks daily
- Concurrent use of any biguanide medication (other than metformin as a study
medication)
- Patients with ≥ grade 2 diarrhea at baseline, malabsorption syndrome or unable to
swallow oral medication
- Previous or concurrent malignancies, except non-melanoma skin cancers, unless
curatively treated and with no evidence of recurrence for ≥ 5 years.
- Use of any investigational agent within 28 days prior to registration.
Gender
Female
Minimum Age
18 Years
Maximum Age
75 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Pamela J Goodwin, MD |
Principal Investigator |
MOUNT SINAI HOSPITAL |
Location
Facility |
London Regional Cancer Program London Ontario Canada |
St. Michael's Hospital Toronto Ontario M5B 1N9 Canada |
Mount Sinai Hospital Toronto Ontario M5G 1X5 Canada |
Princess Margaret Hospital Toronto Ontario M5G 2M9 Canada |
Windsor Regional Cancer Centre Windsor Ontario N8W 2X3 Canada |
Location Countries
Country
Canada
Verification Date
2017-05-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Metformin
Capecitabine
Taxane
Arm Group
Arm Group Label
Metformin
Arm Group Type
Active Comparator
Description
Metformin plus standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).
Arm Group Label
Placebo
Arm Group Type
Placebo Comparator
Description
Placebo and standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study First Submitted
February 18, 2011
Study First Submitted Qc
March 4, 2011
Study First Posted
March 8, 2011
Last Update Submitted
April 5, 2018
Last Update Submitted Qc
April 5, 2018
Last Update Posted
April 6, 2018
ClinicalTrials.gov processed this data on December 06, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.