Evaluation of Metformin, Targeting Cancer Stem Cells for Prevention of Relapse in Gynecologic Patients
The primary objective of this study is to determine if metformin administered in combination with chemotherapy to women with advanced ovarian, primary peritoneal or fallopian tube cancer will improve recurrence-free survival at 18 months compared to controls.
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Evaluation of Metformin, Targeting Cancer Stem Cells for the Prevention of Relapse in Patients With Stage IIC/III/IV Ovarian, Fallopian Tube, and Primary Peritoneal Cancer|
- Improved Recurrence-Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]Determine if metformin administered in combination with chemotherapy to women with advanced ovarian, primary peritoneal or fallopian tube cancer will improve recurrence-free survival (RFS) at 18 months compared to historical controls.
- Overall Survival [ Time Frame: 6 years ] [ Designated as safety issue: No ]Determine if metformin therapy is associated with an improvement in overall survival at 2 years compared to historical controls.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
Other Name: Fortamet, Glucophage, Glumetza, Riomet
Despite 70% remission rates with surgery and chemotherapy, the majority of patients with stage III/IV ovarian cancer will relapse and die of their disease. This is consistent with a cancer stem cell (CSC) model in which a few residual treatment resistant stem cells persist and initiate disease recurrence. Laboratory studies indicate therapies targeting CSC will greatly improve cancer outcomes. We have recently characterized a population of CSC in ovarian cancer. Importantly, similar to that observed in breast cancer, we have found that the diabetes drug metformin can restrict ovarian CSC growth and proliferation. In addition metformin increases tumor cell sensitivity to chemotherapy. Consistent with this, epidemiologic studies demonstrate that diabetic patients with ovarian cancer taking metformin have better outcomes than those not taking metformin. However, metformin has not been tested as an anti-cancer stem cell agent in ovarian cancer. Thus we propose to perform a phase II clinical trial using metformin as an anti-cancer stem cell agent in ovarian cancer patients. Patients who plan to receive primary surgical debulking will initiate metformin therapy prior to surgery and then continue after surgery along with chemotherapy. Patients who will be treated neoadjuvantly will initiate metformin with chemotherapy prior to surgery and then continue both metformin and chemotherapy after surgery. Tumor specimens will be acquired for all patients at the time of primary surgery. The primary objective of this study will be to determine if metformin improves the recurrence-free survival (RFS) of patients relative to historical controls. Secondary objectives of this study will be: (a) to compare the amount of CSC in primary tumor specimens in metformin treated patients versus matched controls from our tumor bank, (b) to determine if metformin improves overall survival relative to historical controls, (c) to confirm the safety of metformin in non-diabetic ovarian cancer patients, and (d) as laboratory studies indicate that metformin is most active in p53 mutant cells and p53 is mutated in ~50% of ovarian cancers, we will assess whether response rates correlate with p53 mutation status. If successful, this well tolerated FDA approved drug could be immediately translated into phase III trials and impact patient outcomes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01579812
|Contact: Cancer Answer Line||Telephone: 1-800-865-1125|
|United States, Michigan|
|University of Michigan||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Ronald J. Buckanovich, MD, PhD||University of Michigan|