Metformin Hydrochloride in Preventing Relapse in Patients with Stage IIC/III/IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IITreatmentActive19 to 79HUM00047900
NCI-2012-00384, HUM 47900, UMCC 2011.037, NCT01579812

Trial Description

Summary

This phase II trial studies how well metformin hydrochloride works in preventing the return of cancer after a period of improvement (relapse) in patients with stage IIC, III, or IV ovarian, fallopian tube, or primary peritoneal cancer. Metformin hydrochloride may reduce the growth of cancer stem cells, which are believed to be the cause of cancer relapse.

Further Study Information

PRIMARY OBJECTIVES:

I. Determine if metformin (metformin hydrochloride) 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 matched historical controls.

II. Compare the percentage and absolute number of cancer stem cells (CSC) in primary tumor specimens in metformin treated patients compared to matched non-treated controls from our tumor bank.

SECONDARY OBJECTIVES:

I. Determine if metformin therapy is associated with an improvement in overall survival at 2 years compared to matched historical controls.

II. Confirm the safety of metformin in non-diabetic patients with ovarian cancer.

III. Correlate numbers of CSC in primary tumor specimens and patient recurrence-free survival.

TERTIARY OBJECTIVES:

I. Assess tumor protein 53 (p53) mutation status and response to metformin.

OUTLINE:

Patients receiving primary surgical debulking followed by adjuvant chemotherapy receive metformin hydrochloride orally (PO) once daily (QD) for 3 days and then twice daily (BID) until 48 hours before surgery. Following surgery, patients receive metformin hydrochloride PO QD for 3 days and then BID beginning 7 days before the initiation of adjuvant chemotherapy and continuing until the last course of chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients treated with neoadjuvant chemotherapy receive metformin hydrochloride PO QD for 3 days and then BID with the initiation of chemotherapy continuing until 48 hours before surgery. Following surgery, if additional adjuvant therapy is indicated, patients receive metformin hydrochloride PO QD for 3 days and then BID beginning 7 days before the initiation of adjuvant chemotherapy (3-6 courses) and continuing until the last course of chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4 months for 1 year.

Eligibility Criteria

Inclusion Criteria:

Patients with potential diagnosis of ovarian, fallopian, or primary peritoneal cancer; care plan including surgical debulking and traditional adjuvant or neo-adjuvant chemotherapy (6-9 cycles of platinum and taxane based therapy)

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Serum creatinine < 1.4 mg/dL

Bilirubin < 1.5 times upper limit of normal (ULN)

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 X ULN in case of liver metastases

ALT or AST < 2.5 X ULN in the absence of liver metastases

Ability to understand and complete written informed consent

Mentally, physically, and geographically able to undergo treatment and follow up

Exclusion Criteria:

Patients with diabetes mellitus; (patients with only a history of gestational diabetes will be allowed to be included in the study)

Metformin use in the last 6 months

A known hypersensitivity to metformin

A history of metabolic acidosis, including ketoacidosis or increased risk of lactic acidosis

Pregnancy or lactation

Patients who have any severe and/or uncontrolled medical conditions

Patients with a history of renal disease

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)

Patients receiving any other investigational agents

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

University of Michigan Comprehensive Cancer Center

  • National Cancer Institute
Ronald Buckanovich, Principal Investigator

Trial Sites

U.S.A.

Michigan
Ann Arbor

University of Michigan Comprehensive Cancer Center

Ronald J. Buckanovich
Ph: 734-764-2395
Email: ronaldbu@umich.edu

Ronald J. Buckanovich
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01579812

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.