A Trial of Standard Chemotherapy With Metformin (vs Placebo) in Women With Metastatic Breast Cancer

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

Sponsors

Lead Sponsor: Ozmosis Research Inc.

Collaborator: Breast Cancer Research Foundation

Source Ozmosis Research Inc.
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 August 22, 2011
Completion Date March 26, 2018
Primary Completion Date July 14, 2016
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: Metformin

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: Placebo

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

Canada

Verification Date

May 2017

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Metformin

Type: Active Comparator

Description: Metformin plus standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).

Label: Placebo

Type: Placebo Comparator

Description: Placebo and standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov