Study of Biomarkers Associated With Fatigue in Patients With Early-Stage Breast Cancer Treated With Metformin or Placebo on NCIC-CTG-MA.32

Study Overview
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Brief Summary
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RATIONALE: Studying samples of blood in the laboratory from patients with breast cancer may help doctors learn more about changes that occur in DNA and identify biomarkers related to fatigue. PURPOSE: This research study is studying biomarkers associated with fatigue in patients with early-stage breast cancer treated with metformin or placebo on NCIC-CTG-MA.32.

Detailed Description
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OBJECTIVES: To prepare, separate into components, and store the blood specimens at the NSABP Serum Bank at Baylor College of Medicine Breast Center for future DNA, RNA, and plasma analysis, and to analyze specific proinflammatory cytokines, genetic polymorphisms, and RNA expression arrays in collaborating laboratories at University of California, Los Angeles (UCLA). To examine the association between markers of inflammation and symptoms of fatigue among patients with and without exposure to metformin hydrochloride. To examine the relationship between single nucleotide polymorphism (SNPs) in the promoter regions of IL-1 and IL-6 and symptoms of fatigue with and without exposure to metformin hydrochloride. To examine RNA expression profiles in relationship to fatigue and compare the pattern of expression in patients with and without exposure to metformin hydrochloride. To determine the biological and behavioral predictors of fatigue in breast cancer patients in the five years post-randomization. To determine whether metformin is associated with reductions in inflammatory markers and corresponding decreases in fatigue. (Exploratory) OUTLINE: This is a multicenter study. Patients' serum and plasma, collected at baseline and at 6, 12, and 24 months after NCIC CTG MA.32 randomization, are analyzed for inflammatory markers, DNA polymorphisms, and RNA expression arrays by ELISA, TaqMan PCR, and RT-PCR. Patients complete the Fatigue Symptom Inventory (symptoms associated with fatigue, sleep disturbance, depression, and endocrine therapy) at baseline and periodically during study.

Official Title
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Biobehavioral Mechanisms of Fatigue in Patients Treated on NCIC CTG MA.32: A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer

Conditions
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Breast Cancer, Depression, Fatigue, Sleep Disorders

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for the MA.32.F Study before being enrolled. The patient must be female. The patient must reside in the United States or Canada. The patient must be English-speaking. The patient must be eligible for randomization in the MA.32 treatment trial. (Participation in the MA.32 QOL study is permitted but not required.) The patient must not have started taking MA.32 study therapy. The patient must have completed primary breast radiation therapy at least two weeks prior to enrollment in MA.32.F. Exclusion Criteria MA.32 study therapy has been initiated. Currently receiving radiation therapy or additional radiation therapy is planned for initiation after starting MA.32 study therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1: Metformin<br>850 mg orally twice a day for 5 years | Drug: Metformin<br> <br> |
| Group 2: Placebo<br>One caplet orally twice a day for 5 years | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Questionnaire scores from patient reported outcome battery regarding fatigue, stress, sleep, depression, and general quality of life |  | Collected at baseline and 6, 12, 24, and 36 months from randomization | 
| Questionnaire scores from patient reported comorbid conditions and behavioral risks |  | Collected at baseline and 6, 12, 24, and 36 months from randomization | 
| Biological correlates of fatigue (medical and demographic characteristics of pts.) | Biological correlates (medical) will be collected at these timepoints. Standard demographics will be collected at baseline only. | Collected at baseline and 6, 12, 24, and 36 months from randomization | 
| DNA polymorphisms |  | Collected at baseline | 
| Changes in RNA gene expression |  | Collected at baseline and 6, 12, and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatigue, sleep disorders, depression, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer