Pan-VEGFR/TIE2 Tyrosine Kinase Inhibitor CEP-11981 in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study
• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Eastern Cooperative Group (ECOG) performance status =< 1
• Patient must have progressive disease while receiving androgen deprivation therapy (ADT) defined by any one of the following as per the PCWG3 criteria for PSA, measurable or non-measurable (bone) disease and must have a castrate serum testosterone level (i.e. =< 50 ng/dL) at screening: * PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value >= 2.0 ng/mL * Measurable disease (by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1): >= 20% increase (with an absolute increase of at least 5 mm) in the sum of diameters of all measurable lesions or the development of one or more new lesions; the short axis of a target lymph node must be more than 15 mm to be assessed for change in size * Non-measurable (bone) disease: The appearance of two or more new areas of uptake on bone scan consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, computed tomography [CT] or magnetic resonance imaging [MRI])
• Documented histologically confirmed adenocarcinoma of the prostate
• Metastatic prostate cancer (M1) as documented by appropriate medical imaging (i.e. computed tomography [CT]-scan, positron emission tomography [PET] scan or bone scan)
• Treatment failure of either abiraterone and/or enzalutamide per PCWG3 criteria for PSA, measurable disease or non-measurable (bone) disease
• Willingness to use contraception by a method that is deemed effective by the investigator throughout the treatment period and for at least 30 days following the last dose of therapy
• Willingness and ability to comply with study procedures and follow-up examination
• Able to swallow and retain oral medication
• Willingness and ability to undergo mandatory tumor biopsy at baseline and week 8/cycle 3
• Willingness and ability to undergo mandatory whole blood sample collections at baseline, days 8, 15, and 22 in the first cycle, and then monthly

Exclusion Criteria

• Current systemic therapy (other than a gonadotrophin releasing hormone [GnRH] agonist/antagonist) for CRPC including: * CYP-17 inhibitors (e.g. ketoconazole, abiraterone) * Antiandrogens (e.g. bicalutamide, nilutamide) * Second generation antiandrogens (e.g. enzalutamide, ARN-509, Galeterone) * Immunotherapy (e.g. sipuleucel-T, ipilimumab) * Chemotherapy (e.g. docetaxel, cabazitaxel)
• Prior chemotherapy (e.g. docetaxel, cabazitaxel) for CRPC; prior docetaxel administered in the castrate-sensitive space is allowed
• Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc.) within the past year
• Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
• Absolute neutrophil count (ANC) less than 1500/mm^3
• Platelet count less than 100000/mm^3
• Hemoglobin less than 9 g/dL
• Bilirubin greater than 1.5 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) greater than 2.0 times the ULN in the absence of known hepatic metastases
• Aspartate aminotransferase (AST) greater than 2.0 times the ULN in the absence of known hepatic metastases
• ALT or AST greater than 3.0 times the ULN in the presence of known hepatic metastases
• The patient has a serum creatinine value greater than 1.5 mg/dL
• The patient has active brain metastases
• The patient is currently on warfarin or heparin therapy
• The patient has any pre-existing coagulopathy, recent hemoptysis, gross hematuria or gastrointestinal bleeding
• The patient has a history of a clinically significant cardiovascular or cerebrovascular event within 6 months prior to study entry
• The patient has uncontrolled hypertension defined as a blood pressure measurement greater than 150 mm Hg systolic or 90 mm Hg diastolic with medication
• The patient has received any investigational drug within the past 4 weeks
• The patient has previously been enrolled in the study or received ESK981
• The patient has known hypersensitivity to gelatin or lactose monohydrate
• The patient has taken a medication known to be a potent inducer of CYP1A2, CYP2C8, or CYP3A4 within 4 weeks prior to the first dose of study drug
• The patient has taken a medication known to be a potent inhibitor of CYP1A2, CYP2C8, or CYP3A4 within 2 weeks prior to the first dose of study drug