Tremelimumab with or without Olaparib in Treating Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Inclusion Criteria

• Provision of informed consent prior to any study specific procedures
• Patients must have recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma); histologic documentation of the original primary tumor is required via the pathology report
• Patients must have archival tissue, 10-20 slides, available for review and testing
• Patients must have measurable disease as defined by RECIST; this is defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes which must have short axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements
• All therapy (except hormonal therapy) directed at the malignant tumor must be discontinued at least 21 days prior to registration
• Any hormonal therapy directed at the malignant tumor must be discontinued at least 7 days prior to registration; continuation of hormone replacement therapy is permitted
• PRIOR THERAPY: * Patients must have had at least one prior taxane-platinum-based chemotherapeutic regimen for management of primary disease; the platinum could be carboplatin or cisplatin; the taxane could be paclitaxel, docetaxel, or nab-paclitaxel * Patients must have had a treatment-free interval following last line platinum-based therapy of less than 12 months, have progressed during platinum-based therapy, or had persistent disease after a platinum-based regimen * Patients may have received hormonal therapy for treatment of recurrent disease; this will not be counted as a cytotoxic regimen * Initial treatment may have included non-cytotoxic agents (biologic/targeted agents, such as bevacizumab) * Patients are allowed to have received prior therapy with tumor vaccines, immune checkpoint blockade (except anti-CTLA-4), or other cancer immunotherapy * Patients are allowed to have received one line of prior treatment with a PARP inhibitor
• Unlimited number of prior treatment lines, provided Gynecologic Oncology Group (GOG)/Eastern Cooperative Oncology Group (ECOG) status is 0-1
• Stable central nervous system (CNS) disease that has been adequately treated and is not under active treatment allowed
• Neuropathy (sensory and motor) less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) grade 1 acceptable
• Patients must be capable of taking and absorbing oral medications
• Patients should be free of active infection requiring antibiotics
• Normal coagulation parameters (prothrombin time [PT], activated partial thromboplastin time [aPTT])
• Human immunodeficiency virus (HIV), human T-cell lymphotropic virus type 1 (HTLV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV) negative
• No systemic oral steroids administered within 28 days prior to initiating treatment on protocol; topical, ocular, and nasal steroids are allowed, as are those applied to mucus membranes
• No prior or currently active autoimmune disease requiring management with systemic immunosuppression; this includes inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia or immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, sarcoidosis, or other rheumatologic disease including Addison’s disease, Grave’s disease, Hashimoto’s thyroiditis, hypophysitis, uveitis); asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable; active vitiligo or alopecia, or a history of vitiligo or alopecia is acceptable
• No active major medical or psychosocial problems that could be complicated by study participation
• No history of other malignancies within the prior five years (excluding a history of non-invasive cancers that have been adequately treated in the opinion of the protocol chair; examples include ductal carcinoma in situ, carcinoma in situ of the cervix, superficial non-melanoma skin cancer, superficial bladder cancer, or tamoxifen-related endometrial cancer that has been adequately treated)
• Hemoglobin >= 9.0 g/dL and no blood transfusions in the 28 days prior to enrollment
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (measured within 28 days prior to administration of study treatment)
• No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear (measured within 28 days prior to administration of study treatment)
• White blood cells (WBC) > 3 x 10^9/L (measured within 28 days prior to administration of study treatment)
• Platelet count >= 100 x 10^9/L (measured within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 X institutional upper limit of normal unless liver metastases are present in which case it must be =< 5 x ULN (measured within 28 days prior to administration of study treatment)
• Serum creatinine =< 1.5 X institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
• Patients must have a life expectancy >= 16 weeks
• Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1; postmenopausal is defined as: * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50 * Radiation-induced oophorectomy with last menses > 1 year ago * Chemotherapy-induced menopause with > 1 year interval since last menses * Surgical sterilization (bilateral oophorectomy or hysterectomy)
• Patients of child bearing potential who are sexually active must agree to the use of two highly effective forms of contraception from the time of informed consent through 6 months after last dose of study drug(s)
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria

• No histologic documentation of EOC
• Histology consistent with primary peritoneal mesothelioma rather than primary peritoneal serous carcinoma
• No archival or newly biopsied tissue available for analysis
• Prior therapy with monoclonal antibody (mAb) against CTLA-4
• Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 4 weeks from the last dose prior to study treatment; the patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug
• Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
• Untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy
• Patients with myelodysplastic syndrome/acute myeloid leukemia
• History of symptomatic gastrointestinal disorder within the last five years resulting in bleeding or chronic or frequent diarrhea
• Signs or symptoms of gastrointestinal obstruction
• Active or history of diverticulitis; diverticulosis is permitted
• Requirement for chronic parenteral hydration/nutrition
• History of bleeding disorder or diathesis
• Serious or non-healing wound, ulcer, bone fracture, or osteonecrosis of the jaw
• Major surgical procedure within 28 days of study enrollment, or anticipated while on study
• History of chronic inflammatory or autoimmune disease
• Systemic oral corticosteroid treatment within 28 days prior to initiating treatment on study except as detailed above
• Clinically significant cardiovascular disease
• Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment
• Persistent toxicities (>= CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy
• Resting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on high resolution CT scan or any psychiatric disorder that prohibits obtaining informed consent
• Breast feeding women
• Patients with a known hypersensitivity to olaparib or tremelimumab