Evaluation of Metformin, Targeting Cancer Stem Cells for Prevention of Relapse in Gynecologic Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Michigan Cancer Center
Sponsor:
Information provided by (Responsible Party):
Ronald Buckanovich, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01579812
First received: March 30, 2012
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Drug: Metformin
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 104
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)
Arms Assigned Interventions
Experimental: Metformin Drug: Metformin

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

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.

  Eligibility

Ages Eligible for Study:   19 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with potential diagnosis of ovarian, fallopian, or primary peritoneal cancer.
  2. Care plan including surgical debulking and traditional adjuvant or neo-adjuvant chemotherapy (6-9 cycles of platinum and taxane based therapy).
  3. Eastern Cooperative Oncology Group performance status 0-2.
  4. Age > 18 years or < 80 years.
  5. Adequate renal function (serum creatinine <1.4mg/dL).
  6. Adequate liver function (bilirubin < 1.5 times ULN).

    • Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) < 5 times the upper limit of normal in case of liver metastases.
    • ALT or AST < 2.5 times the ULN in absence of liver metastases.
  7. Ability to understand and complete written informed consent.
  8. Mentally, physically, and geographically able to undergo treatment and follow up.

Exclusion Criteria:

  1. Patients diabetes mellitus. (Patients with only a history of gestational diabetes will be allowed to be included in the study.)
  2. Metformin use in the last 6 months.
  3. A known hypersensitivity to metformin.
  4. A history of metabolic acidosis, including ketoacidosis or increased risk of lactic acidosis.
  5. Pregnancy or Lactation.
  6. Patients who have any severe and/or uncontrolled medical conditions.
  7. Patients with a history of renal disease.
  8. Patients with other known active malignancy (excluding adequately treated basal cell / squamous cell skin cancer, in situ cancer, or other cancer for which the patient has been disease free for 2 years).
  9. Patients receiving any other investigational agents.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579812

Contacts
Contact: Cancer Answer Line Telephone: 1-800-865-1125

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Ronald Buckanovich
Investigators
Principal Investigator: Ronald J. Buckanovich, MD, PhD University of Michigan
  More Information

No publications provided

Responsible Party: Ronald Buckanovich, Assistant Professor, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01579812     History of Changes
Other Study ID Numbers: UMCC 2011.037, HUM 47900
Study First Received: March 30, 2012
Last Updated: June 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Additional relevant MeSH terms:
Peritoneal Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014