A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer

Status
Active
Cancer Type
Breast Cancer
Trial Phase
Phase III
Eligibility
18 to 74, Male and Female
Study Type
Biomarker/Laboratory analysis
Treatment
NCD ID
NCT01101438
Protocol IDs
MA32 (primary)
U10CA077202
CAN-NCIC-MA.32
CDR0000669788
NCIC-MA.32
Study Sponsor
NCIC-Clinical Trials Group

Summary

This study is looking at whether Metformin, an agent that is commonly used to treat diabetes, can decrease or affect the ability of breast cancer cells to grow and whether Metformin will work with other therapies to keep cancer from recurring. Health Canada has not approved the sale or use of Metformin to treat breast cancer, although they have approved its use in this clinical trial. Although Metformin is approved by the FDA for the treatment of diabetes, its use in breast cancer is considered investigational.

Objectives

OBJECTIVES:

Primary

  • To compare invasive disease-free survival of patients with early-stage breast cancer treated with metformin vs placebo in addition to standard adjuvant therapy.

Secondary

  • To compare overall survival of these patients.
  • To compare distant disease-free survival of these patients.
  • To compare breast cancer-free interval in these patients.
  • To compare invasive disease-free survival of patients who are hormone receptor-negative (both estrogen receptor and progesterone receptor).
  • To compare changes in body mass index in these patients.
  • To compare adverse events in these patients.
  • To compare other medical endpoints, including a new diagnosis of diabetes mellitus or cardiovascular hospitalization (including an emergency room visit or overnight stay) or death (stroke or myocardial infarction), in these patients.
  • To compare health-related quality of life measured using the EORTC QLQ-C30 (supplemented by a trial-specific checklist), the Block Alive Screener, and physical activity items from the Nurses Health Study Questionnaire II on a subset of these patients.
  • To compare embedded correlative science outcomes including plasma insulin and molecular markers of metformin action in these patients.
  • To compare metabolic parameters including metabolic components of the insulin resistance syndrome as defined by the ATP III criteria in a subset of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to hormone-receptor status (estrogen receptor- and/or progesterone receptor- positive vs both receptors negative), body mass index (= 30 vs > 30 kg/m²), HER2 status (positive vs negative), and prior chemotherapy (any vs none). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral metformin hydrochloride twice daily (once daily in weeks 1-4). Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral placebo twice daily (once daily in weeks 1-4). Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

Blood and tumor samples are collected periodically for correlative studies.

Patients may complete quality-of-life, physical activity, and diet questionnaires at baseline and at 6, 12, 24, 36, 48, and 60 months.

After completion of study treatment, patients are followed annually.

Treatment Sites in Georgia


Longstreet Cancer Center - Gainesville
725 Jesse Jewel Parkway
3rd Floor
Gainesville, GA 30501
www.longstreetclinic.com

Study Coordinator:
Patti Rotunda
(770) 219-8826

Doctors:

Timothy M. Carey MD
Anup K. Lahiry MD
Richard J. LoCicero MD
Charles H. Nash, III MD, FACP

Northeast Georgia Diagnostic Clinic - Gainesville
1240 Jesse Jewell Parkway
Suite 500
Gainesville, GA 30501
www.ngdc.com

Study Coordinator:
Patti Rotunda
(770) 219-8826

Doctors:

Padma C. Nadella MD
Saloni H. Tanna MD
Christina A. Saurel MD

Pearlman Cancer Center at South Georgia Medical Center
2501 North Patterson Street
Valdosta, GA 31602
229-259-4628
www.sgmc.org

Doctors:

Eric B. Anderson MD
Samuel N Ofori MD

Surgical Oncology of Northeast Georgia
690 Medical Park Lane
Gainesville, GA 30501
www.drkendixon.com

Study Coordinator:
Patti Rotunda
(770) 219-8826

Doctors:

P. Kendal Dixon MD

Toccoa Cancer Center
1640 Falls Road
Toccoa, GA 30577
www.nghs.com

Study Coordinator:
Patti Rotunda
(770) 219-8826

Doctors:

Geoffrey J. Weidner MD