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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Dose-Finding Pilot Study of XL184 in Men With Castrate-Resistant Prostate Cancer and Bone Metastases

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: cabozantinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose level 0: cabozantinib 40 mg daily | Drug: cabozantinib<br>* Cabozantinib PO QD<br>* Other names: XL84;|
| Experimental: Cohort 2<br>Dose level -1: cabozantinib 20 mg daily | Drug: cabozantinib<br>* Cabozantinib PO QD<br>* Other names: XL84;|
| Experimental: Expansion cohort<br>Dose level 0: cabozantinib 40 mg daily | Drug: cabozantinib<br>* Cabozantinib PO QD<br>* Other names: XL84;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Response in Bone Scan From Baseline to 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. | Baseline and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Castration Resistant, Bone Metastases