Defactinib Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients with Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Inclusion Criteria

• Patients must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, diagnosed within 6 months of completing their most recent platinum-containing chemotherapy; histologic documentation of the original primary tumor is required via a pathology report; * Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.)
• All patients must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
• Patients of childbearing potential must have a negative serum pregnancy test prior to study entry and be practicing an effective form of contraception
• Absolute neutrophil count >= 1,500 cells/uL equivalent to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03) grade 1
• Platelets >= 100,000/uL equivalent to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03) grade 1
• Serum creatinine level less than or equal to 1.5 x institutional upper limit normal (ULN) (CTCAE v4.03 grade 1)
• Glomerular filtration rate (GFR) > 60 mL/min
• Serum bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4.03 grade 1)
• Neuropathy (sensory and motor) less than or equal to CTCAE v4.03 grade 1
• All persistent clinically significant toxicities from prior chemotherapy must be less than or equal to grade 1
• Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least three weeks prior to registration
• Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, noncytotoxic agents or extended therapy administered after surgical or non-surgical assessment
• Patients must have NOT received more than two total prior lines of cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens
• Patients may have received one additional non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) hormones, monoclonal antibodies, cytokines, and small molecule inhibitors of signal transduction
• Patients must be considered platinum resistant according to standard GOG criteria, which defines patients as having had a treatment-free interval following platinum of less than 6 months

Exclusion Criteria

• Platinum-refractory ovarian, fallopian tube, or primary peritoneal carcinoma
• Known second primary or prior malignancy diagnosed within 5 years of study start date (other than previously treated non-melanoma skin cancer)
• Current treatment with chemotherapy or radiation therapy; any prior therapy directed at the malignant tumor, including biologic and immunologic agents, must be discontinued at least three weeks prior to registration
• History of treatment with known kinase inhibiting agents
• History of gastrointestinal fistula, hemorrhage, perforation or peptic ulcer disease
• Patients who are pregnant or breastfeeding