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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 14-000924
    NCT ID: NCT02122185
    Sponsor Protocol Number: UC-IRB13-1235

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • 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
  • 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: subjects must have histologically confirmed carcinoma consistent with ovarian, fallopian tube, or primary peritoneal carcinoma (any of these three are referred to in this protocol as "ovarian cancer [OvCA]" OR a cytological diagnosis of carcinoma); the following histologic subtypes are included: serous, endometrioid, undifferentiated, clear cell, mixed, transitional, malignant Brenner tumor or adenocarcinoma not otherwise specified (NOS); subjects eligible for this study may be in one of three surgical categories: status post primary debulking surgery; undergoing neoadjuvant chemotherapy at a site not participating in correlative tissue collection sub study OR undergoing neoadjuvant chemotherapy at a site participating in correlative tissue collection sub study
  • ELIGIBILITY CRITERIA FOR REGISTRATION: 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
  • ELIGIBILITY CRITERIA FOR REGISTRATION: subjects for whom neoadjuvant chemotherapy followed by interval cytoreductive surgery is planned must have fine needle aspirate (FNA) or other cytology showing adenocarcinoma OR core biopsies OR surgically directed biopsies showing adenocarcinoma AND CA125 over 250 OR CA125:CEA ratio > 25 OR CA =< 250 with no evidence of GI cancer; they should have presumed stage III or IV disease, generally based on abdominal carcinomatosis, omental caking, pleural effusions or ascites
  • ELIGIBILITY CRITERIA FOR REGISTRATION: the subject and her physician must agree to six cycles of one of the standard of care regimens allowed on this protocol; these regimens (starting dosage) include:
    • IV paclitaxel 175 mg/m^2 and carboplatin area under the curve (AUC) 5-6 every 21 days
    • IV docetaxel 75 mg/m^2 and carboplatin AUC 5-6 every 21 days
    • IV paclitaxel 80 mg/m^2 day 1, 8, and 15 and carboplatin AUC 5-6 day 1 every 21 days
      • Use of granulocyte colony stimulating factor is permitted, but additional chemotherapy agents (e.g. gemcitabine) or biologic agents (e.g. bevacizumab) are not; dose modifications for patients over age 70 are allowable as outlined in the protocol
  • ELIGIBILITY CRITERIA FOR REGISTRATION: ECOG performance status =< 2
  • ELIGIBILITY CRITERIA FOR REGISTRATION: Leukocytes >= 3,000/mcL
  • ELIGIBILITY CRITERIA FOR REGISTRATION: absolute neutrophil count >= 1,500/mcL
  • ELIGIBILITY CRITERIA FOR REGISTRATION: platelets >= 100,000/mcL
  • ELIGIBILITY CRITERIA FOR REGISTRATION: total bilirubin =< upper normal institutional limits (except for patients with Gilbert's disease who are eligible despite elevated serum bilirubin level)
  • ELIGIBILITY CRITERIA FOR REGISTRATION: AST(SGOT)/ALT(SGPT) =< 2.0 × institutional upper limit of normal
  • ELIGIBILITY CRITERIA FOR REGISTRATION: creatinine =< OR institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
  • ELIGIBILITY CRITERIA FOR REGISTRATION: blood glucose =< 126 mg/dL fasting or =< 140 mg/dL nonfasting
  • ELIGIBILITY CRITERIA FOR REGISTRATION: women of child-bearing potential must agree to use an effective method of birth control on trial, as the safety of metformin in pregnancy has not been established; an effective method of birth control includes surgical sterilization of woman or her partner, abstinence, or two barrier methods (e.g. condom plus diaphragm); hormonal methods of birth control are not permitted on this study
  • ELIGIBILITY CRITERIA FOR REGISTRATION: ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • EXCLUSION CRITERIA FOR PRE-REGISTRATION
  • 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 are excluded from this study
  • EXCLUSION CRITERIA FOR REGISTRATION: mucinous adenocarcinoma, borderline tumors
  • EXCLUSION CRITERIA FOR REGISTRATION: subjects who will undergo intraperitoneal chemotherapy
  • EXCLUSION CRITERIA FOR REGISTRATION: subjects receiving neoadjuvant chemotherapy for whom interval debulking surgery (assuming adequate response to therapy) is not planned
  • EXCLUSION CRITERIA FOR REGISTRATION: subjects receiving chemotherapy regimens not specified in the inclusion criteria
  • EXCLUSION CRITERIA FOR REGISTRATION: 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)
  • EXCLUSION CRITERIA FOR REGISTRATION: 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
  • EXCLUSION CRITERIA FOR REGISTRATION: patients who are receiving any other investigational agents
  • EXCLUSION CRITERIA FOR REGISTRATION: subjects with comorbidities which would lead to a clinical expectation that they will not survive two years for reasons other than ovarian cancer
  • EXCLUSION CRITERIA FOR REGISTRATION: concurrent active invasive malignancy or one previously diagnosed with a greater than 30% chance of recurrence in the next two years
  • EXCLUSION CRITERIA FOR REGISTRATION: history of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin
  • EXCLUSION CRITERIA FOR REGISTRATION: 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
  • EXCLUSION CRITERIA FOR REGISTRATION: uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • EXCLUSION CRITERIA FOR REGISTRATION: pregnant or nursing women are excluded from this study

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Sean Dowdy, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

.
CLS-20145302

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