This is a single-arm, open-label Phase II multi-institutional trial in 30 patients that have been molecularly selected based on that their tumors possess alterations in molecular targets of cabozantinib. Patients will be treated be continuously until they develop radiographic progression or discontinue cabozantinib for toxicity. If 6 or more out of 12 subjects with particular mutation or gene amplification show progression prior to 6 months, accrual for the particular genomic alteration may close. In addition, a series of correlative studies will be performed including tissue biopsies in order to further define the mechanisms of cabozantinib anti-tumor action in prostate cancer and identify surrogate markers of response.~This research study is being done because additional effective treatments are needed for prostate cancer that has spread and is growing despite hormone suppression. Prior studies indicate that Cabozantinib may be effective in a subset of these participants, but that has not yet been determined.~About 30 subjects will take part in this study at 4 participating sites. We expect to enroll approximately 20 participants at Weill Cornell Medicine and approximately 3-5 subjects per participating site. All subjects participating in this study will be treated with Cabozantinib. All subjects will continue to take LHRH analogue therapy.~Once eligible participants will be enrolled on the trial for approximately approximately 12 months. At that point, subjects will switch to long-term follow up for two years after removal from the study or until death, whichever occurs first.~Study related procedures can be combined with routine Standard of Care (SOC) visits. These will include obtaining medical history, vitals, routine blood collection, radiographic imaging (CT, MRI and Bone scan), EKG and between 2 and 4 weeks after starting therapy, a tumor biopsy is required. This will be done with a needle by local sedation by an Interventional Radiologist.
The purpose of this study is to determine what effects (good and bad) cabozantinib has in treatment of patients with metastatic castrate resistant prostate cancer (mCRPC).~The hypothesis for this trial is that cabozantinib has anti-tumor activity in a molecularly-selected group of patients with CRPC.