• Age \>18 years.

• Documented histological or cytological diagnosis of prostate carcinoma.

• Evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan)

• \- Patients with liver metastases must have biopsy proven evidence of metastatic prostate cancer in the liver.

• Agree to undergo a biopsy of at least one metastatic site or primary prostate prior to beginning therapy. Adequate archival metastatic tissue can be used if available in lieu of a biopsy if done when patient had CRPC and within 6 months of the start of treatment.

• Agree to undergo a biopsy of at least one metastatic site or primary prostate after 3 weeks of therapy (biopsy must be between day 21 and day 24 of treatment). Re-biopsy of same pre-treatment biopsy soft tissue site especially liver metastases is preferred.

• Serum testosterone level less than 50 ng/dl. Subjects 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 treatment.

• Documented progressive metastatic CRPC based on at least one of the following criteria:

‣ PSA progression according to Prostate Cancer Working Group 3 (PCWG3) criteria

⁃ Objective radiographic progression, according to PCWG3 criteria

• ECOG performance status of 0-1

• Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless specified below or AE(s) are clinically nonsignificant and/or stable on supportive therapy.

⁃ Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:

∙ Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support

‣ White blood cell count ≥ 2500/mm\^3 (≥ 2.5 GI/L)

‣ Platelets ≥ 100,000/mm\^3 (≥ 100 GI/L) without transfusion

‣ Hemoglobin ≥ 9 g/dL (≥ 90 g/L)

‣ Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)

‣ Serum albumin ≥ 2.8 g/dl

‣ Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation:

‣ If urine dipstick is positive, then: Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)

⁃ Patients without liver metastases must have evidence of amplification or activating mutation of selected targets of cabozantinib (including MET, KIT, RET, VEGFR-1, VEGFR-2, VEGFR-3, FLT3, AXL, TRKB, or TIE2) by at least one of the following:

∙ DNA sequencing of metastatic tumor biopsy specimen or cfDNA test

‣ RNA sequencing of metastatic tumor biopsy specimen

‣ Commercial cell-free DNA assay

‣ Overexpression by IHC on metastatic tumor biopsy specimen

⁃ Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment

⁃ Capable of understanding and complying with the protocol requirements and must have signed the informed consent document