Metformin and Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT02122185 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB13-1235NCI-2014-00860
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 10

Brief Summary

This randomized phase II trial studies how well metformin hydrochloride and combination chemotherapy works in treating patients with stage III-IV ovarian, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride may help carboplatin, paclitaxel and docetaxel work better by making tumor cells more sensitive to the drugs. Studying samples of blood and tissue in the laboratory from patients receiving metformin hydrochloride may help doctors learn more about the effects of metformin hydrochloride on cells. It may also help doctors understand how well patients respond to treatment. Giving metformin hydrochloride together with combination chemotherapy may kill more tumor cells.

Conditions

Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Time to disease progression or death from any cause. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 and Gynecological Cancer Intergroup (GCIG) criteria. For example, progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to 6 years

Secondary Outcomes (3)

• Time to Biochemical (CA-125) Progression, Radiological Progression, or Death.

  Up to 6 years

• Overall Survival

  Up to 6 years

• Number of Participants With Adverse Events

  Up to 6 years

Study Arms (2)

Metformin plus chemotherapy

EXPERIMENTAL

Patients receive metformin hydrochloride PO BID and standard chemotherapy for 6 -8 cycles. Treatment with metformin hydrochloride continues for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: metformin hydrochloride; Drug: Chemotherapy

Placebo plus chemotherapy

PLACEBO COMPARATOR

Patients receive placebo PO BID and standard chemotherapy for 6 -8 cycles. Treatment with placebo continues for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: placebo; Drug: Chemotherapy

Interventions

metformin hydrochloride DRUG

Given PO

Also known as: Glucophage

Metformin plus chemotherapy

placebo DRUG

Given PO

Also known as: PLCB

Placebo plus chemotherapy

Chemotherapy DRUG

Participants will receive standard chemotherapy (6-8 cycles). Specific regimen to be given was chosen from among six protocol-specified options at the discretion of their treating physician.

Metformin plus chemotherapy; Placebo plus chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ELIGIBILITY CRITERIA FOR PRE-REGISTRATION
• A reasonable suspicion of ovarian cancer by the treating oncologist is required, evidenced by abdominal carcinomatosis, omental caking, pleural effusions or ascites AND an elevated CA125 \> 250 OR CA125:carcinoembryonic antigen (CEA) ratio \> 25 OR CA125 =\< 250 with no evidence of gastrointestinal (GI) cancer
• Aged 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< upper normal institutional limits (except for patients with Gilbert's disease who are eligible despite elevated serum bilirubin level)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.0 × institutional upper limit of normal
• Creatinine =\< institutional upper limit of normal (ULN) OR creatinine clearance \>= 60 mL/min/1.73 m\^2
• Blood glucose =\< 126 mg/dL fasting or =\< 140 mg/dL nonfasting
• Signed written pre-registration informed consent document
• ELIGIBILITY CRITERIA FOR REGISTRATION:
• Histologically confirmed carcinoma consistent with ovarian, fallopian tube, or primary peritoneal carcinoma
• Subjects undergoing primary debulking surgery must have stage III or IV disease and have undergone surgery to include, at a minimum, removal of the uterus, ovaries and fallopian tubes; these patients may be optimally debulked (less than 1 cm residual disease) but must have grossly visible macroscopic residual disease OR be suboptimally debulked

You may not qualify if:

• Subjects with known diabetes and those taking metformin, sulfonylureas, thiazolidinediones or insulin for any reason
• Patients who are receiving any other investigational agents
• Subjects with comorbidities that would limit their two year survival for reasons other than ovarian cancer
• Concurrent active invasive malignancy or one previously diagnosed with a greater than 30% chance of recurrence in the next two years
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin
• Subjects must not have conditions associated with increased risk of metformin-associated lactic acidosis, including New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, alcoholic liver disease, or habitual intake of 3 or more alcoholic beverages per day
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active major infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or nursing women
• mucinous adenocarcinoma, borderline tumors
• subjects who will undergo intraperitoneal chemotherapy
• subjects receiving neoadjuvant chemotherapy for whom interval debulking surgery (assuming adequate response to therapy) is not planned
• subjects should not be participating in other clinical trials of interventions designed to reduce risk of ovarian cancer recurrence or plan to receive off -protocol maintenance therapy (e.g. paclitaxel or bevacizumab)
• subjects with known diabetes, fasting glucose over 126 mg/dL or random glucose over 140 mg/dL and those taking metformin, sulfonylureas, thiazolidenediones or insulin for any reason
• patients who are receiving any other investigational agents
• subjects with comorbidities which would lead to a clinical expectation that they will not survive two years for reasons other than ovarian cancer

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (10)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Mitchell Cancer Institute - University of South Alabama

Mobile, Alabama, 36604, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

NCH Medical Group- Northwest Community Hospital

Arlington Heights, Illinois, 60005, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Brenner Tumor; Pleural Effusion, Malignant; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Metformin; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Fibroepithelial; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases; Fallopian Tube Diseases; Carcinoma; Endocrine Gland Neoplasms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Therapeutics

Results Point of Contact

• Title: Theodore Karrison, PhD
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

708-925-6771

Study Officials

• Seiko Yamada

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 24, 2014
• Study Start: February 25, 2015
• Primary Completion: October 27, 2022
• Study Completion: October 8, 2024
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Locations

US (10)