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

NCT01310231 | Completed Phase 2 Results DMC

• 1 other identifier: OZM-027
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic Breast Cancer; Metformin

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival.

  Scans will be repeated every 9 weeks. Local follow up for survival will continue until all patients have died or for a maximum total follow up of 3 years, which ever occurs first. The two study arms will be compared in an intent to treat fashion using Cox proportional hazard analysis, with the stratification variables included in the model. Treatment discontinuation for toxicity or other reasons will be considered an event.

  From date of randomization to first documented progression or death, which ever occurs first, assessed up to 3 years.

Secondary Outcomes (9)

• Overall Response Rate

  From baseline until time of best response, assessed up to 3 years

• Number of Participants With Grade 1 or 2 Adverse Events

  Up to 30 days after end of study

• Number of Participants With Grade 3 or 4 Adverse Events

  Up to 30 days after end of study

• EORTC Quality of Life Measures

  From baseline to cycle 2 of chemotherapy

• Change in Fasting Glucose (mmol/L)

  Baseline to Cycle 2

Study Arms (2)

Metformin

ACTIVE COMPARATOR

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

Drug: Metformin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Metformin 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.

Metformin

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ozmosis Research Inc.: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (5)

London Regional Cancer Program

London, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1N9, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

Related Publications (1)

• 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.

  PMID: 31472446 RESULT

Related Links

• Study Results

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Limitations include relatively small sample size, with associated imbalances in frequency of visceral (vs nonvisceral) metastatic disease, in HER2 positive and negative cancers, and in type of chemotherapy received in the metformin vs placebo arms.

Results Point of Contact

• Title: Pamela Goodwin/PI
• Organization: Mount Sinai Hospital

Pamela.goodwin@sinaihealth.ca

416 586-8211

Study Officials

• Pamela J Goodwin, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2011
• First Posted: March 8, 2011
• Study Start: August 22, 2011
• Primary Completion: July 14, 2016
• Study Completion: March 26, 2018
• Last Updated: April 14, 2021
• Results First Posted: April 14, 2021

Record last verified: 2021-03

Locations

CA (5)