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Patients must have a recurrent, advanced, or metastatic pure clear cell carcinoma of ovarian, fallopian tube, primary peritoneal, or extra-renal origin |
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All patients must submit representative tissue from their malignancy |
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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 |
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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 |
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No prior anti-PD-1, PD-L1 or CTLA-4 antibody |
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Age ≥ 18 |
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ECOG performance status 0 to 1 |
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Participants must have normal organ and marrow function as defined below |
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leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total |
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bilirubin within normal institutional limits EXCEPTIONS: conjugated hyperbilirubinemia |
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Gilbert's syndrome, both of which will allow a total bilirubin <3.0mg/dL <5xULN is liver |
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metastases are present A value below the LLN is acceptable if confirmed appropriate by the |
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treating MD AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine ≤ 1.5 |
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X ULN (upper limit of normal) OR creatinine clearance ≥50 mL/min |
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Adequate thyroid function within 28 days prior to registration defined as serum TSH in |
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normal range. Patients on thyroid hormone supplementation are allowed provided the |
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serum TSH is within normal limits |
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Reproductive status |
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Subjects must have a resting baseline O2 saturation by pulse oximetry of ≥92% at rest |
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This should be documented within two weeks of registration |
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Women of childbearing potential (WOCBP) must use method(s) of contraception. Given |
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Women must not be breastfeeding (document for all) |
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there is insufficient information to assess teratogenicity (preclinical studies have |
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not been done), a highly effective method(s) of contraception (failure rate of less |
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than 1% per year) is required as determined by the treating investigator. WOCBP must |
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Ability to understand and the willingness to sign a written informed consent document |
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follow instructions for birth control. For all women who discontinue protocol |
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treatment, contraception should be continued for five months following the last dose |
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of therapy |
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WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L |
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or equivalent units of HCG) within 7 days prior to the start of registration |
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Women who are not of childbearing potential (ie, who are postmenopausal (lack of |
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menses > 24 months) or surgically sterile) and azospermic men do not require |
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contraception |
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Men who are sexually active with WOCBP must use any contraceptive method with a |
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failure rate of less than 1 % per year. The investigator shall review contraception |
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methods and the time period that contraception must be followed |
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Men that are sexually active with WOCBP must follow instructions for birth control |
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when the half life of the investigational drug is greater than 24 hours, contraception |
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should be continued for a period of 7 months after discontinuation of treatment |
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Participants who are receiving any other investigational agents
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History of severe hypersensitivity reaction to any monoclonal antibody
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Pregnant women are excluded from this study
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Planned concomitant, non-protocol directed anti-cancer therapy during the trial
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Participants who have had prior therapy with nivolumab or with an anti-PD-1
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anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
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specifically targeting T-cell co-stimulation or immune check point pathways
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Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
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nitrosoureas or mitomycin C) prior to entering the study. Patients using endocrine
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therapy as treatment for their index cancer must be off of treatment for one week (7
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days) prior to entering the study
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Participants who have not recovered from clinically significant adverse events to
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<grade 2 and which are related to prior treatment agents administered
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Participants with known brain metastases are excluded from this clinical trial because
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of their poor prognosis and because they often develop progressive neurologic
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dysfunction that would confound the evaluation of neurologic and other adverse events
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Uncontrolled intercurrent illness including, but not limited to, ongoing or active
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infection requiring antibiotics, symptomatic congestive heart failure, unstable angina
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pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that
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would limit compliance with study requirements
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Patients with a history of other invasive malignancies, with the exception of
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non-melanoma skin cancer are excluded if there is any evidence of other malignancy
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being present within the last three years. However, patients with a malignancy that is
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not-likely to require treatment in the next 2 years, such as a completely resected
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early stage breast cancer, are eligible
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Patients who have received prior chemotherapy within the last three years for any
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other cancer other than for clear cell cancer
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In order for patients with known history of testing positive for human
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immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) to be
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eligible, they must be on a stable highly active antiretroviral therapy (HAART)
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regimen, have CD4 counts > 350, with no detectable viral load on quantitative PCR
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within 4 weeks of registration
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Patients with treated hepatitis virus infections (Hepatitis B or Hepatitis C) are
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eligible if they have been definitively treated for 6 months, have no detectable viral
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load on quantitative PCR, and LFTs meet eligibility requirements within 4 weeks of
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screening
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Patients with active autoimmune disease or history of autoimmune disease that might
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recur, which may affect vital organ function or require immune suppressive treatment
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including systemic corticosteroids, should be excluded
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Patients should be excluded if they have a condition requiring systemic treatment with
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either corticosteroids (>10 mg daily prednisone equivalents) or other
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immunosuppressive medications within 14 days of day 1 study drug administration
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Any other medical condition that will prevent the safe administration of study drugs
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in the opinion of the treating physician
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Grade ≥2 peripheral neuropathy
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