A Trial of Standard Chemotherapy With Metformin (vs Placebo) in Women With Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Metformin; Placebo
Intervention 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.; 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 MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: Female
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Metastatic Breast Cancer; Metformin

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.
    

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.