Study of Cabozantinib in Combination With Abiraterone in Chemotherapy-Naïve Subjects With Bone-Metastatic Castration-Resistant Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This study is designed to evaluate the safety and efficacy of combining abiraterone (with prednisone) with cabozantinib in chemotherapy-naïve subjects with bone-metastatic castration-resistant prostate cancer (CRPC).

Official Title
-----------------
A Randomized Phase 2 Study of Cabozantinib (XL184) in Combination With Abiraterone in Chemotherapy Naïve Subjects With Bone-Metastatic Castration-Resistant Prostate Cancer

Conditions
-----------------
Prostate Cancer, Castration Resistant Prostate Cancer, Prostatic Neoplasms

Intervention / Treatment
-----------------
* Drug: cabozantinib
* Drug: abiraterone
* Drug: prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate. Must be surgically or medically castrated (serum testosterone levels less than or equal to 50 ng/dL) Must have castration-resistant prostate cancer (CRPC) with disease progression during LHRH therapy or after a surgical bilateral orchiectomy. Bone metastasis related to prostate cancer Adequate organ and marrow function Capable of understanding and complying with the protocol requirements and signed the informed consent document Sexually active subjects and their partners must agree to use medically accepted methods of barrier contraception (eg, male condom or female condom) as well as one other medically accepted method of contraception during the course of the study treatment and for 4 months after the last dose of study treatment. Exclusion Criteria: Any prior treatment with abiraterone, enzalutamide, or any investigational agents blocking androgen receptor (AR) or androgen synthesis. Any prior treatment with cabozantinib or participation in a prior clinical trial of cabozantinib. Any prior cytotoxic therapy (including estramustine) or biologic therapy for the treatment of prostate cancer (a few exceptions will be allowed) Any prior radionuclide therapy (eg, samarium 153, strontium 89, alpharadin) Use of investigational agent within 28 days Any pathological finding consistent with small cell carcinoma of the prostate Known brain metastases or cranial epidural disease Diagnosis of another malignancy within 2 years, except for superficial non-melanoma skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib arm 1<br>Subjects randomized to this arm will receive cabozantinb 40 mg daily with abiratarone and prednisone | Drug: cabozantinib<br>* Tablets taken orally<br>* Other names: XL184;Drug: abiraterone<br>* Tablets taken orally daily<br>* Other names: abiraterone acetate;Drug: prednisone<br>* Tablets taken orally twice daily<br>|
| Experimental: Cabozantinib arm 2<br>Subjects randomized to this arm will receive cabozantinib 20 mg daily with abiraterone and prednisone | Drug: cabozantinib<br>* Tablets taken orally<br>* Other names: XL184;Drug: abiraterone<br>* Tablets taken orally daily<br>* Other names: abiraterone acetate;Drug: prednisone<br>* Tablets taken orally twice daily<br>|
| Experimental: Cabozantinib arm 3<br>Subjects randomized to this arm will receive cabozantinb 20 mg every other day with abiraterone and prednisone | Drug: cabozantinib<br>* Tablets taken orally<br>* Other names: XL184;Drug: abiraterone<br>* Tablets taken orally daily<br>* Other names: abiraterone acetate;Drug: prednisone<br>* Tablets taken orally twice daily<br>|
| Active Comparator: Abiraterone only arm (4)<br>Subjects randomized to this arm will receive abiraterone with prednisone only | Drug: abiraterone<br>* Tablets taken orally daily<br>* Other names: abiraterone acetate;Drug: prednisone<br>* Tablets taken orally twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic progression free survival (PFS) | PFS is defined as the time from randomization to the earlier of the following events: disease progression or death due to any cause | Up to 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CRPC, castration resistant prostate cancer, prostate cancer