Cabozantinib (XL184) in Men With Castrate-Resistant Prostate Cancer

Phase 1

Completed

Brief Summary: Cabozantinib (XL184) is a new drug that is being developed to treat cancer. Cabozantinib works by blocking the "angiogenesis," or the growth of new blood vessels, to the tumor. This is similar to how several other cancer drugs work but in addition Cabozantinib also blocks other pathways that may be responsible for allowing cancer cells to become resistant to these other "anti-angiogenic" treatments. So far cabozantinib has been investigated in treating brain cancer and a rare form of thyroid cancer. This study will explore lower doses of cabozantinib with the goal to find the most effective, safe, and tolerable dose without undesirable side effects.

Detailed Description: Cabozantinib will be taken by mouth daily. The first five treatment cycles will be 21 days. All cycles after that will be 42 days long. Patients will keep a diary to record study drug dosing.

During the screening phase patients will receive a physical exam, blood and urine tests, a bone scan, a CT of the abdomen and pelvis, and an MRI scan of total body. On Day 1 of each cycle patients will receive a physical exam and blood and urine tests. Bone scan, CT and MRI scans will be performed at the start of cycles 3 and 5, and then repeated once every 12 weeks.

Patients will continue to receive study treatment as long as they are receiving benefit from the treatment, do not experience any severe or unmanageable side effects, and disease does not get any worse.

Recruitment & Eligibility

Inclusion Criteria

Histologically confirmed prostate adenocarcinoma
Bone metastases confirmed by bone scan
Current androgen deprivation therapy
Castration-resistant disease based on progression in bone and/or PSA progression
Recovered from toxicities related to prior treatment, except alopecia, lymphopenia, other non-clinically significant adverse events
Life expectancy of greater than 3 months
Normal organ and marrow function
Capable of understanding and complying with the protocol requirements
Agree to use medically accepted methods of contraception
Able to swallow capsules

Exclusion Criteria

More than two prior chemotherapy regimens for metastatic prostate cancer
Known untreated, symptomatic or uncontrolled brain metastases
Serious or unhealed wound
Treatment with anticoagulants
Previously identified allergy or hypersensitivity to components of the study treatment formulation
History of a different malignancy unless disease-free for at least 5 years, or basal or squamous cell carcinoma of the skin
Current antiretroviral therapy
Uncontrolled hypertension
Uncontrolled intercurrent illness

Arm && Interventions

Group	Intervention	Description
Cohort 1	cabozantinib	Dose level 0: cabozantinib 40 mg daily
Cohort 2	cabozantinib	Dose level -1: cabozantinib 20 mg daily
Expansion cohort	cabozantinib	Dose level 0: cabozantinib 40 mg daily

Primary Outcome Measures

Name	Time	Method
Partial Response in Bone Scan From Baseline to Week 6	Baseline and Week 6	Bone scans will be centrally reviewed and categorized based on comparison of week 6 and baseline imaging. Partial response is defined as 30% or greater decrease in bone scan lesion area from baseline to week 6. An adaptive response design to determine the lowest effective cabozantinib dose among three dose levels (dose level +1, dose level 0 and dose level +1) will be employed.

Secondary Outcome Measures