Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Ozmosis Research Inc.
Sponsor:
Collaborator:
Breast Cancer Research Foundation
Information provided by:
Ozmosis Research Inc.
ClinicalTrials.gov Identifier:
NCT01310231
First received: February 18, 2011
Last updated: October 29, 2012
Last verified: October 2012

February 18, 2011
October 29, 2012
March 2011
March 2013   (final data collection date for primary outcome measure)
Progression free survival. [ Time Frame: From date of randomization to first documented progression or death, which ever occurs first, assessed up to 3 years. ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01310231 on ClinicalTrials.gov Archive Site
  • Overall response rate [ Time Frame: From baseline until time of best response, assessed up to 3 years ] [ Designated as safety issue: No ]
    Overall response rate in patients with measureable disease based upon RECIST Version 1.1. Patients will have scans repeated every 9 weeks and overall review of response across the study will be done every 6 months. The overall response rate is defined as number of patients with a best overall response of CR or PR, as a proportion of all patient with measurable disease at baseline. The response rate between arms will be compared using logistic regression with treatment as factor, adjusted for strata.
  • 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. [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
    Adverse events will be graded using CTCAE Version 4.0. Frequency tables will be produced per arm of the treatment emergent adverse event rates.The treatment emergent adverse event rates will be further summarized by maximum toxicity grade per patient during treatment.
  • Quality of life and treatment related symptoms [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    The symptom checklist and the symptom related EORTC measures will be compared between arms using frequency tables.
  • 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). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Physiologic parameters (fasting insulin, glucose, HOMA) will be transformed to normality prior to analyses. The parameters will be modeled over time using graphical methods to find an appropriate functional form. Parameters will be compared between arms over time using a linear mixed-effect model with terms for arm, time and a group-by-time interaction and treating patients as random effects.
  • Immunohistochemical predictors of metformin benefit and to explore changes in these variables in women who undergo serial biopsies of their metastases. [ Time Frame: Baseline and 3 weeks. ] [ Designated as safety issue: No ]
    Immunohistochemical analysis of different markers (IR, LKB1, phosphorylated AKT, S6K, ribosomal protein S6, 4E-BP1, and stathmin) pre and post first cycle of chemotherapy with metformin as well as in the original tumour tissue. Change in the phospho-markers of PI3K/mTOR will be summarized before and after the first cycle of chemotherapy with a focus on detection between the study arms.
  • Gene expression predictors of potential metformin benefit including exploration of changes in these variables in women who undergo serial biopsies of their metastases [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Gene expression profiles in the baseline (original tumour) and, when available, pre and post cycle 1 chemotherapy will be established and change in gene signature pre and post chemotherapy will be explored.
Same as current
Not Provided
Not Provided
 
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 or Second Line Chemotherapy With Anthracycline, Taxane, Platinum or Capecitabine Based Regimens

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Metastatic Breast Cancer
  • Drug: 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.

  • 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.

  • Active Comparator: Metformin
    Metformin plus standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).
    Intervention: Drug: Metformin
  • Placebo Comparator: Placebo
    Placebo and standard chemotherapy (containing anthracyclines, platinum, taxanes or capecitabine; first or second line).
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
78
September 2015
March 2013   (final data collection date for primary outcome measure)

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.
Female
18 Years to 75 Years
No
Contact: Pamela J Goodwin, MD 416-586-8605 pgoodwin@mtsinai.on.ca
Canada
 
NCT01310231
OZM-027
Yes
Dr. Pamela Goodwin, M.D., M.Sc., F.R.C.P.C., Mount Sinai Hospital
Ozmosis Research Inc.
Breast Cancer Research Foundation
Principal Investigator: Pamela J Goodwin, MD Mount Sinai Hospital, New York
Ozmosis Research Inc.
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP