BrUOG 354 Nivolumab +/- Ipilimumab for Ovarian and Extra-renal Clear Cell Carcinomas

Inclusion Criteria

• •Patients must have a recurrent, advanced, or metastatic pure clear cell carcinoma of ovarian, fallopian tube, primary peritoneal, or extra-renal origin.
• •All patients must submit representative tissue from their malignancy.
• •Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• •Patients with a clear cell carcinoma of ovarian, fallopian or primary peritoneal origin must have progressed after at least one prior platinum and taxane based chemotherapy regimen. Patients with extra-renal clear cell cancer (including other GYN) cancers must have progressed after at least one prior regimen for advanced/metastatic disease. Radiation therapy (including the use of chemotherapy as a radiosensitizer) will not count as a prior systemic regimen.
• •No prior anti-PD-1, PD-L1 or CTLA-4 antibody.
• •Age ≥ 18
• •ECOG performance status 0 to 1
• •Participants must have normal organ and marrow function as defined below:
• •leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin within normal institutional limits EXCEPTIONS: conjugated hyperbilirubinemia; Gilbert's syndrome, both of which will allow a total bilirubin \<3.0mg/dL \<5xULN is liver metastases are present A value below the LLN is acceptable if confirmed appropriate by the treating MD AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine ≤ 1.5 X ULN (upper limit of normal) OR creatinine clearance ≥50 mL/min
• •Adequate thyroid function within 28 days prior to registration defined as serum TSH in normal range. Patients on thyroid hormone supplementation are allowed provided the serum TSH is within normal limits.
• •Subjects must have a resting baseline O2 saturation by pulse oximetry of ≥92% at rest. This should be documented within two weeks of registration.
• •Reproductive status:
• •Women of childbearing potential (WOCBP) must use method(s) of contraception. Given there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required as determined by the treating investigator. WOCBP must follow instructions for birth control. For all women who discontinue protocol treatment, contraception should be continued for five months following the last dose of therapy.
• •WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of registration.
• •Women who are not of childbearing potential (ie, who are postmenopausal (lack of menses \> 24 months) or surgically sterile) and azospermic men do not require contraception.
• •Women must not be breastfeeding (document for all).
• •Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1 % per year. The investigator shall review contraception methods and the time period that contraception must be followed.
• •Men that are sexually active with WOCBP must follow instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 7 months after discontinuation of treatment.
• •Ability to understand and the willingness to sign a written informed consent document.
• •Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded.
• •Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of day 1 study drug administration.
• •Any other medical condition that will prevent the safe administration of study drugs in the opinion of the treating physician.
• •Planned concomitant, non-protocol directed anti-cancer therapy during the trial.
• •Grade ≥2 peripheral neuropathy