Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100
Condition: Prostate Cancer; Castration Resistant Prostate Cancer; Pain; Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: cabozantinib; prednisone
Intervention description: Tablets taken orally once-daily; Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
Intervention MeSH terms: Prednisone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1028.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate cancer; castration resistant prostate cancer; bone pain; CRPC

Summary:

      This study will evaluate the effect of cabozantinib compared to prednisone on overall
      survival in men with previously treated metastatic castration-resistant prostate cancer with
      bone-dominant disease who have experienced disease progression on docetaxel-containing
      chemotherapy and abiraterone or MDV3100.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological diagnosis of castration resistant prostate cancer (serum
             testosterone less than 50 ng/dL).

          -  Evidence of bone metastasis related to prostate cancer on bone scans.

          -  Received prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone
             or MDV3100 treatment and has evidence of prostate cancer progression on each agent
             independently.

          -  Maintenance of LHRH agonist or antagonist unless treated with orchiectomy.

          -  Recovered from toxicities related to any prior treatments, unless the toxicities are
             clinically non significant or easily manageable.

          -  Adequate organ and marrow function.

          -  Capable of understanding and complying with the protocol requirements and signed the
             informed consent form.

          -  Sexually active fertile patients and their partners must agree to use medically
             accepted methods of contraception (eg, 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.

        Exclusion Criteria:

          -  Prior treatment with cabozantinib.

          -  Treatment with docetaxel, abiraterone, or MDV3100 in the last 2 weeks; or with any
             other type of cytotoxic or investigational anticancer agent in the last 2 weeks.

          -  Radiation within 4 weeks (excluded if to mediastinum) or radionuclide treatment within
             6 weeks of randomization.

          -  Known brain metastases or cranial epidural disease.

          -  Requires concomitant treatment, in therapeutic doses, with anticoagulants.

          -  Requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone,
             phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St.
             John's Wort).

          -  Uncontrolled, significant intercurrent illness including, but not limited to,
             cardiovascular disorders, gastrointestinal disorders, active infections, non-healing
             wounds, recent surgery.

          -  Clinically significant hematemesis or hemoptysis, or other signs indicative of
             pulmonary hemorrhage in the last 3 months, or history of other significant bleeding in
             the past 6 months.

          -  Cavitating pulmonary lesion(s) or a lesion invading or encasing a major blood vessel.

          -  QTcF > 500 ms within 7 days of randomization.

          -  Unable to swallow capsules or tablets.

          -  Previously-identified allergy or hypersensitivity to components of the study treatment
             formulations.

          -  Another diagnosis of malignancy requiring systemic treatment within 2 years of
             randomization.