Evaluation of Metformin, Targeting Cancer Stem Cells for Prevention of Relapse in Gynecologic Patients
Condition: Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
MeSH terms: Peritoneal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Metformin
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Fortamet, Glucophage, Glumetza, Riomet
Intervention MeSH terms: Metformin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ovarian, Fallopian Tube, and Primary Peritoneal Cancer