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

NCT ID: NCT01310231

Last Updated: 2021-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-22
• Study Completion Date: 2018-03-26

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.

Detailed Description

A double blind Phase II randomized study of metformin versus (vs) placebo in non-diabetic women on first to fourth line chemotherapy with anthracycline, taxane, platinum, capecitabine or vinorelbine based regimens for metastatic or unresectable locally advanced breast cancer (BC). Patients were randomized to receive metformin 850 mg tablets or placebo once daily for two days as ramp-up, followed by one tablet twice a day for the duration of the study. Randomization was stratified by line of chemotherapy (1st, 2nd, 3rd and 4th line) and hormone receptor status (ER and/or PgR positive versus both negative). All patients were required to have measureable or non-measureable, but evaluable metastases at study entry. Metformin or placebo was to be continued until disease progression, even if chemotherapy was changed or stopped prior to disease progression. Recruitment took place at five sites in Ontario, Canada: Mount Sinai Hospital, Princess Margaret Cancer Centre, St. Michael's Hospital, Toronto and London Regional Cancer Centre, London.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

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

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Metformin

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Breast Cancer Research Foundation

OTHER

Sponsor Role: collaborator

Ozmosis Research Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pamela J Goodwin, MD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

London Regional Cancer Program

London, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Countries

Canada

References

Pimentel I, Lohmann AE, Ennis M, Dowling RJO, Cescon D, Elser C, Potvin KR, Haq R, Hamm C, Chang MC, Stambolic V, Goodwin PJ. A phase II randomized clinical trial of the effect of metformin versus placebo on progression-free survival in women with metastatic breast cancer receiving standard chemotherapy. Breast. 2019 Dec;48:17-23. doi: 10.1016/j.breast.2019.08.003. Epub 2019 Aug 22.

Reference Type: RESULT

PMID: 31472446 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/31472446/

Study Results

Other Identifiers

OZM-027

Identifier Type: -

Identifier Source: org_study_id