A Randomized PHASE II/III STUDY OF PACLITAXEL/CARBOPLATIN/METFORMIN (NSC#91485) VERSUS PACLITAXEL/CARBOPLATIN/PLACEBO AS INITIAL THERAPY FOR MEASURABLE STAGE III OR IVA, STAGE IVB, OR RECURRENT ENDOMETRIAL CANCER NCT#02065687
This study is being carried out under the sponsorship of the Gynecologic Oncology Group (GOG), an organization dedicated to clinical research in the field of gynecologic cancer. The GOG is funded by the Federal Government through the National Cancer Institute (NCI). WHY IS THIS STUDY BEING DONE? The purpose of this study is to find out if the drug combination of paclitaxel, carboplatin and metformin works better than paclitaxel and carboplatin alone in treating your type of cancer and to find out what side effects are caused by treatment with these drugs. The combination of paclitaxel, carboplatin and metformin in the treatment of advanced or recurrent endometrial cancer is investigational. In order to better determine if the addition of metformin to paclitaxel and carboplatin helps better treat endometrial cancer, half of the women in this study will receive metformin with paclitaxel and carboplatin and the other half will receive a placebo with paclitaxel and carboplatin. A placebo is a tablet or pill with no active ingredients. Metformin is a medication used to treat diabetes that is widely used as first line therapy for type II diabetes. Both obesity and diabetes are strong risk factors for endometrial cancer. Recent evidence suggests that metformin may also kill cancer cells and be helpful in both the treatment and prevention of many cancers, including endometrial cancer. Metformin is FDA approved, but not for cancer treatment and is being used as an investigational agent in this study. You will also undergo measurements of your hip to waste ratio to better understand the relationship of body size to your cancer. In addition to the treatment part of this study, the researchers plan to test samples of your tumor and some of your blood. The purpose of this research is to determine whether the presence of certain proteins and genes predict if this drug will be an effective treatment for endometrial cancer. Also, in addition to the treatment part of this study, the researchers want to know your view of how your life has been affected by cancer and its treatment. As part of this study you will be asked to complete questionnaires about your quality of life. HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? About 540 patients may eventually take part in this study. After approximately 240 patients have been entered into the study, the information so far gathered about how well the treatment works will be analyzed to determine if the remaining patients should be entered onto the study.
Treatment Location: N/A
Primary Objective To determine if the addition of metformin to the standard regimen of carboplatin and paclitaxel prolongs progression-free survival (PFS) in women with advanced or recurrent endometrial cancer (Phase II). To determine if the addition of metformin to the standard regimen of carboplatin and paclitaxel prolongs overall survival (OS) in the same population if a phase III study is conducted. Both clinical trials (Phase II and III) will utilize OS as a primary endpoint if a phase III trial is opened. Secondary Objectives To estimate the proportion of patients (pts.) with objective response (RR) in the population of patients with measurable disease by treatment. To estimate the duration of response in the population of patients with measurable disease who respond by treatment. To estimate overall survival (OS) and relative hazards of death for each treatment arm if the study stops after the phase II trial is completed. If the study continues with a phase III clinical trial, then PFS will be a secondary endpoint. To determine the nature, frequency and degree of toxicity as assessed by CTCAE for each treatment arm. To estimate possible differences in RR, PFS, OS, and toxicity rates for the treatment regimens by the patients’ level of obesity. Translational Research Objectives Integrated Biomarker Research Objectives To test whether PIK3CA mutations/amplifications, PTEN mutations or PIK3R1/PIK3R2 mutations have a lower hazard of progressionor death (PFS endpoint) among patients who are treated with metformin. To test whether higher expression of MATE2 is associated with a lower hazard of progression or death (PFS endpoint) among patients who are treated with metformin. Exploratory Biomarker Objectives To explore the association of metabolic factors (i.e. BMI, hip-to-waist ratio, diabetes status, HgbA1C, fasting insulin and glucose levels, HOMA scores) with treatment response to metformin/paclitaxel/carboplatin, PFS and OS To test whether genomic profiles (i.e.PIK3CA mutations/amplifications PTEN mutations or PIK3R1/PIK3R2 mutations) differ between the tumors of obese and non-obese EC patients. To correlate expressionof key targets of the insulin/IGF-1/mTOR signaling pathway (p-IGF1R, P-S6 and p-4EBP-1) with treatment response to metformin/paclitaxel/carboplatin, PFS, OS and obesity status. To determine if the genetic variants of the metformin transporters correspond with treatment response to metformin/paclitaxel carboplatin PFS and OS. Patient Reported Outcome Objectives To estimate differences in physical functioning, physical activity, and fatigue between treatment arms. Hypothesis: Patients assigned to the metformin treatment arm will report better physical functioning and physical activity and less fatigue compared to patients assigned to the placebo treatment arm. This between-arm difference will be most prominent in the obese patients. To explore the association between metabolic factors (i.e., BMI, hip-towaist ratio, diabetes status, HgbA1C, fasting insulin and glucose levels, HOMA scores) and physical functioning, physical activity, and fatigue. Hypothesis: We postulate that patients with increased BMI, hip-to-waist ratio, diabetes, HgbA1C, fasting insulin and glucose levels, and HOMA scores will report higher rates of health status decline, as measured by physical functioning, physical activity, and fatigue self-report scores.
IRB Review and Approval Date: 08/13/2014
Recruitment Status: Closed
Projected Accrual: N/A
Information and next steps
Phase II/Phase III
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