XL-184+Abiraterone in Post-Chemo CRPC

Study Overview
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Brief Summary
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This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. Investigational means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA (U.S. Food and Drug Administration) may not have approved this drug for use in participants, including people with your type of cancer. In this research study, we are testing the safety of XL184 at different dose levels. XL184 is a new study drug, which is taken by mouth. Laboratory studies have shown that XL184 may prevent tumor growth by stopping the formation of blood vessels inside the tumor and also shrink tumors. This drug has been used in early-stage studies and is also currently being studied in other trials. Information from those other research studies suggests that XL184 may help to slow or stop tumor growth including prostate cancer. We will also be taking blood and urine tests to look at how your body processes the drug.

Detailed Description
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The following procedures will be performed during this study. On Day 1 for every cycle (28 days/4 weeks)-The following will be undertaken prior to initiating study therapy and on day 1 of every subsequent cycle: A medical history, physical exam, performance status, blood tests, urine test. Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants, not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses. We will actively monitor your condition for up to 30 days after you come off the study. If you come off study for a side effect we will monitor your condition until the resolution or stabilization of the side effect

Official Title
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A Dose Finding Clinical Trial of Cabozantinib (XL 184) Administered in Combination With Abiraterone in Castration Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Cabozantinib
* Drug: Abiraterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CRPC with up to 2 prior chemotherapy regimens Progressive disease on CT, MRI or bone scan per mRECIST Has recovered to baseline/CTCAE less than or equal to Grade 1 from toxicities related to prior treatment (except alopecia) Agree to use accepted barrier method of contraception Exclusion Criteria: Cytotoxic chemotherapy within 3 weeks Prior treatment with cabozantinib or other c-MET inhibitor Prior therapy with a lyase inhibitor Concurrent use of hormonal therapies other than LHRH analogue or orchiectomy Received radiation therapy to thoracic cavity or GI tract within 3 months, to bone or brain metastasis within 2 weeks or to any other site within 4 weeks of first dose of study drug Prior treatment with a small molecular kinase inhibitor within 2 weeks of study entry Received another investigational product within 28 days prior to study entry Active brain metastases or epidural disease Requires concomitant treatment in therapeutic doses with warfarin or warfarin-related agents No uncontrolled significant intercurrent or recent 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Cabozantinib and abiraterone | Drug: Cabozantinib<br>* 28 day cycle<br>* Other names: XL 184;Drug: Abiraterone<br>* 28 day cycle<br>* Other names: Zytiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | To define the MTD of cabozantinib in combination with abiraterone | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Definition of a Dosing Regimen | To define a dosing regimen of abiraterone and cabozantinib suitable for further evaluation based on long term toxicity and efficacy data | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castration Resistant, Post Chemotherapy