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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01697566.
PRIMARY OBJECTIVES:
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.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorKaren H. Lu
