Trial of Cabozantinib (XL184) in Castrate-Resistant Prostate Cancer Metastatic to Bone
Condition: Prostate Cancer Metastatic
MeSH terms: Prostatic Neoplasms; Neoplasms
Intervention: Cabozantinib
Intervention description: Cabozantinib is available in capsule form. The dose is 60 mg daily by mouth. Subjects with disease progression at 6 weeks who do not have significant toxicities may remain on therapy for an additional six weeks until a progression is confirmed. Further study drug administration beyond 12 weeks will be at the discretion of the investigator provided that the subject does not have disease progression, does not have unacceptable side effects, does not withdraw from study, or does not have a medical condition or illness that renders the subject unacceptable to receive further study drug.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate; Cancer; Metastatic

Summary:

      The purpose of this study is to look at the effects of cabozantinib on castrate-resistant
      prostate cancer metastatic (cancer that has spread to other parts of the body) to the bone
      and to learn about any side effects caused by taking cabozantinib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically and radiologically confirmed castrate-resistant prostate cancer
             metastatic to bone

          -  Bone metastases which are accessible for biopsy under CT guidance.

          -  Willingness to undergo sequential biopsy of bone lesions.

          -  No prior standard chemotherapy for metastatic disease (neoadjuvant, adjuvant and
             hormonal treatments are excluded).

          -  Participant must have discontinued antiandrogen therapy at least 4 weeks (for
             flutamide and megestrol acetate) or 6 weeks (for bicalutamide or nilutamide) prior to
             the first dose of XL184. Participants currently on LHRH or GnRH agonists can be
             maintained on these agents.

          -  Greater than or equal to 18 years old on day of consent

          -  Participants must be able to care for themselves

          -  Adequate organ and bone marrow function

          -  Participants must be capable of understanding and complying with the protocol
             requirements and has signed the informed consent document.

          -  Men capable of sexual activity will be required to agree to use a condom during sexual
             contact with women having the potential to bear children during their participation in
             the study and for six months after participation.

        Exclusion Criteria:

          -  Prior therapy with cabozantinib

          -  Any other type of investigational agent within 28 days before the first dose of study
             treatment or 5 half-lives of the compound or active metabolite, whichever is longer

          -  No radiation therapy within 14 days of study treatment. No radionuclide treatment
             within two months.

          -  No known brain metastases.

          -  Test results that measure how quickly blood clots need to be adequate for the study

          -  Participants who require concomitant treatment, in therapeutic doses, with
             anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or
             Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (≤
             81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight
             heparin (LMWH) are permitted.

          -  Participants must not have uncontrolled significant illness including but not limited
             to: ongoing or active infection requiring systemic treatment, symptomatic congestive
             heart failure, uncontrolled hypertension , history of hypertensive emergency
             (e.g.encephalopathy) or hypertensive urgency within 6 months of study treatment,
             clinically significant wounds including osteonecrosis, history of organ transplant,
             unstable angina pectoris, stroke within 3 months of study drug, heart attack within 3
             months of study drug, development of clots within blood vessels within 6 months of
             study drug, bleeding from distended veins within 3 months of study drug, any other
             severe or life threatening hemorrhage/bleeding, major surgery within 4 weeks of study
             treatment, clinically significant cardiac arrhythmias, history of bowel obstruction
             within 6 months of study drug or unresolved malabsorption syndrome, untreated bone
             fracture including tumor-related pathologic fracture, anticipated need for major
             surgery during the period of the study.

          -  Corrected QT interval, as measured by an ECG, must be within acceptable protocol
             limits within 28 days of entering the study

          -  Unable to swallow capsules

          -  Unable to undergo MRI

          -  History of another malignant disease within two years with the exception of
             superficial skin or bladder cancer which has been completely resected or carcinoma in
             situ without evidence of invasion.