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

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
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
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
Subject and her physician must agree to six cycles or up to 8 cycles of one of the standard of care regimens allowed on this protocol; these regimens (starting dosage) include:

If < 70 years old:

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

If 70 years or older:

IV paclitaxel 135 mg/m^2 plus IV carboplatin AUC 5 plus optional G-CSF every 21 days
IV paclitaxel 60 mg/m^2 day 1, 8, 15 plus IV carboplatin AUC 5 every 21 days (Day 15 paclitaxel optional)

IV paclitaxel 60 mg/m^2 plus IV carboplatin AUC 2 day 1, 8, and 15 every 21 days

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)
AST(SGOT)/ALT(SGPT) =< 2.0 × institutional upper limit of normal
creatinine =< OR institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
blood glucose =< 126 mg/dL fasting or =< 140 mg/dL nonfasting
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
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

EXCLUSION CRITERIA FOR REGISTRATION:

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 receiving chemotherapy regimens not specified in the inclusion criteria
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
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 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
pregnant or nursing women