A Randomized Phase II, Double Blind, Trial of Standard Chemotherapy With Metformin (vs Placebo) in Women With Metastatic Breast Cancer Receiving First or Second Line Chemotherapy With Anthracycline, Taxane, Platinum or Capecitabine Based Regimens
- 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,
- 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.
- 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
- 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
- Habitual alcohol intake of more than three drinks daily
- Concurrent use of any biguanide medication (other than metformin as a study
- 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.