Metformin Hydrochloride with or without Lifestyle Intervention in Preventing Endometrial Cancer in Obese Post-Menopausal Patients with High Insulin Levels
Basic Trial Information
|Phase III||Behavioral study, Biomarker/Laboratory analysis, Prevention||50 to 60||2011-0739|
TRIAL STATUS: Active
This randomized phase III trial studies metformin hydrochloride with lifestyle intervention to see how well it works compared to metformin chloride or lifestyle intervention alone in preventing endometrial cancer in post-menopausal patients that are obese and have high insulin levels. Metformin hydrochloride may prevent endometrial cancer in patients that are obese and have high insulin levels. Lifestyle intervention may help patients lose weight and increase physical activity. It is not yet known whether giving metformin hydrochloride and lifestyle intervention together or alone is more effective in preventing endometrial cancer.
Further Study Information
I. To evaluate the independent effects of metformin (metformin hydrochloride) and a diet and physical activity intervention on potential surrogate endpoint biomarkers (SEBs) of the endometrium in obese post-menopausal women.
II. Other biomarkers will be examined, including a panel of genes (proliferating cell nuclear antigen [PCNA], insulin-like growth factor receptor type 1 [IGF-IR], retinaldehyde dehydrogenase 2 [RALDH2], secreted frizzled-related protein 4 [sFRP4], survivin, and estrogen induced gene 121 [EIG121]) relevant to estrogen-dependent endometrial proliferation, hyperplasia and cancer using quantitative polymerase chain reaction (Q-PCR); biomarkers specific to the effect of metformin treatment (phosphorylated [phospho]-activated protein kinase catalytic subunit alpha [AMPKa], phospho-acetyl-coA carboxylase [ACC], phospho-mammalian target of rapamycin [mTOR] and phospho-S6 ribosomal protein).
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive escalating doses of metformin hydrochloride orally (PO) once daily (QD) in week 1, twice daily (BID) in week 2, thrice daily (TID) in week 3, and BID in week 4. After week 4, patients continue to receive metformin hydrochloride PO BID.
ARM II: Patients receive escalating doses of placebo PO QD in week 1, BID in week 2, TID in week 3, and BID in week 4. After week 4, patients continue to receive placebo PO BID. Patients also undergo a lifestyle intervention in 16 sessions over 4 months, which comprises discussing ways to manage weight; receiving print materials and worksheets, measuring utensils, a food scale, and a pedometer, and instruction on how to use them; and optional opportunities to participate in supervised exercise.
ARM III: Patients receive metformin hydrochloride as in Arm I, and lifestyle intervention as in Arm II.
ARM IV: Patients receive placebo PO as in Arm II.
In all arms, treatment continues for 4 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 year.
Body mass index (BMI) > or = 30 kg/m^2
Not frankly diabetic, as measured by a fasting blood glucose =< 126 mg/dL
Demonstrate hyperinsulinemia with a quantitative insulin sensitivity check index (QUICK I) value =< 0.357
Zubrod performance scale 0-1
Hemoglobin >= 10 g/dl
Thyroid stimulating hormone (TSH) 0.27 - 4.20 ulU/mL
Menopause as defined as no menses for 1 year and/or follicle-stimulating hormone (FSH) >= 25.8 mIU/ml
Must be able to read, write, and speak English
Must have a primary care provider (PCP)
Prior hysterectomy or endometrial ablation
Alanine aminotransferase (ALT) >= 2.0 x upper limit of normal (ULN)
Serum creatinine >= 1.4 mg/dl
Triglycerides (fasting) >= 400
Known inability to participate in the ongoing appointments for the four months of the study and scheduled follow-up tests
Significant medical or psychiatric history which would make the participant a poor protocol candidate, in the opinion of the principal investigator, for any aspect of study participation including metformin, unsupervised exercise program or dietary behavior change
Participant reported history of congestive heart failure
Prior treatment with metformin
Currently being treated for diabetes or meeting criteria for new diagnosis of diabetes
Known allergy to metformin or other biguanide (Proguanil)
Use of aromatase inhibitors, gonadotropin-releasing hormone (GNRH)-agonists i.e. Lupron, Zoladex within the last 6 months
Use of selective estrogen receptor modulators (SERMS) in the past 6 months, including tamoxifen and raloxifene
Hormone replacement therapy within the last 6 months
Women who have been treated with chemotherapy for prior malignant disease or currently have an untreated malignancy other than non-melanoma skin cancer
Patients who have had prior radiation to the pelvis
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
M D Anderson Cancer Center
- National Cancer Institute
M D Anderson Cancer Center
Karen Hsieh Lu
Karen Hsieh Lu
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01697566
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