Phase I Study of TVB-2640 in Men With Metastatic Castration-Resistant Prostate Cancer

The purpose of this study is to determine what effects (good and bad) Enzalutamide and TVB-2640 have in the treatment of prostate cancer whose prostate cancer has spread to other parts of their body and that has not gotten better with previous treatment. This study is a Phase I clinical trial. Phase I clinical trials test the side effects of an investigational drug or an investigational combination with another drug. "Investigational" means that the drug is still being studied and research doctors are trying to find out more about it. Although Enzalutamide is already being used to treat men with prostate cancer, combining Enzalutamide with TVB-2640 together in patients with prostate cancer is considered experimental. This research study is being done because additional effective treatments are needed for prostate cancer that has spread and is growing despite hormone suppression. By doing this study, the investigators hope to learn if combining Enzalutamide with TVB-2640 can be done safely. Participation in this research will last about 12 to 24 months after enrollment.

Inclusion Criteria:Age >18 years.Diagnosis of metastatic, castration resistant prostate cancerPotential participant must be planning to receive Enzalutamide as their first line of therapy for castration resistant prostate cancer or have previously received up to one line of Abiraterone or an androgen receptor antagonistNo prior treatment with cytotoxic chemotherapyWilling to undergo a tumor biopsy prior to beginning therapy, if recent tissue samples are not availableAgree to undergo a tumor biopsy of at least one metastatic site or primary prostate after ~4 weeks of therapy with both agentsParticipants without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatmentSexually active, fertile participants and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom with spermicide during the course of the study and for 4 months after the last dose of study treatmentCapable of understanding and complying with the protocol requirements and must have signed the informed consent documentExclusion Criteria:Any prior cytotoxic chemotherapy for hormone sensitive prostate cancer.Receipt of any type of biologic, or other systemic anticancer therapy (including investigational) except agents within 4 weeks before first dose of study treatment. Anti-resorptive bone agents are also allowed.Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment for neurological indications at the time of first dose of study treatment.Participants with clinically significant dry eye or corneal abnormalitiesParticipants with a history of seizureCurrently taking certain anticoagulation medications, such as coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)10. The subject has uncontrolled, significant intercurrent or recent Cardiovascular disorders including, but not limited to, the following conditions: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.ii. Uncontrolled hypertension defined as sustained blood pressure (BP) >140 mm Hg systolic or >90 mm Hg diastolic despite optimal antihypertensive treatment.iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before first dose.Inability to swallow tablets.Use of herbal products that may decrease PSA levels within 4 weeks prior to enrollmentPreviously identified allergy or hypersensitivity to components of the study treatment formulations.Diagnosis of another type of cancer within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.