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

Sponsor

Exelixis (Industry)

Overall Status

Terminated

CT.gov ID

NCT01995058

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

2.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Castration Resistant Prostate Cancer Prostatic Neoplasms	Drug: cabozantinib Drug: abiraterone Drug: prednisone	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cabozantinib arm 1 Subjects randomized to this arm will receive cabozantinb 40 mg daily with abiratarone and prednisone	Drug: cabozantinib Tablets taken orally Other Names: XL184 Drug: abiraterone Tablets taken orally daily Other Names: Zytiga(R) abiraterone acetate Drug: prednisone Tablets taken orally twice daily
Experimental: Cabozantinib arm 2 Subjects randomized to this arm will receive cabozantinib 20 mg daily with abiraterone and prednisone	Drug: cabozantinib Tablets taken orally Other Names: XL184 Drug: abiraterone Tablets taken orally daily Other Names: Zytiga(R) abiraterone acetate Drug: prednisone Tablets taken orally twice daily
Experimental: Cabozantinib arm 3 Subjects randomized to this arm will receive cabozantinb 20 mg every other day with abiraterone and prednisone	Drug: cabozantinib Tablets taken orally Other Names: XL184 Drug: abiraterone Tablets taken orally daily Other Names: Zytiga(R) abiraterone acetate Drug: prednisone Tablets taken orally twice daily
Active Comparator: Abiraterone only arm (4) Subjects randomized to this arm will receive abiraterone with prednisone only	Drug: abiraterone Tablets taken orally daily Other Names: Zytiga(R) abiraterone acetate Drug: prednisone Tablets taken orally twice daily

Outcome Measures

Primary Outcome Measures

Radiographic progression free survival (PFS) [Up to 18 months]
PFS is defined as the time from randomization to the earlier of the following events: disease progression or death due to any cause

Other Outcome Measures

Safety and tolerability as assessed by adverse events [Up to 18 months]
Subjects are followed for safety as assessed by adverse events at least through 30 days after the date of a decision to permanently discontinue study treatment.
Pharmacokinetic Pre-dose Plasma Concentrations of both cabozantinib and abiraterone when administered in combination [Days 1-4, Week 3, Week 5, Week 7, Week 9, Week 17, and Week 41]
When administered in combination, both cabozantinib and abiraterone plasma concentrations will be measured prior to dosing on selected visits
Overall survival [Up to 36 months]
Overall survival is defined as the time from randomization to death from any cause.
Bone scan response by computer-aided detection (CAD) [Up to 18 months]
Bone scans will be evaluated by an independent radiology facility for response
Pharmacokinetic Plasma Area Under the Curve (AUC) [Week 5]
For selected subjects, the plasma AUC of cabozantinib and abiraterone will be measured at Week 5

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Scottsdale	Arizona	United States	85258
2	Sedona	Arizona	United States	86336
3	Tucson	Arizona	United States	85710
4	Oxnard	California	United States	93030
5	San Diego	California	United States	92108
6	Aurora	Colorado	United States	80012
7	Aurora	Colorado	United States	80045
8	Athens	Georgia	United States	30607
9	Atlanta	Georgia	United States	30318
10	Peoria	Illinois	United States	61615
11	Wichita	Kansas	United States	67214
12	Las Vegas	Nevada	United States	89148
13	Raleigh	North Carolina	United States	27607
14	Tualatin	Oregon	United States	97062
15	Charleston	South Carolina	United States	29414
16	Greenville	South Carolina	United States	29605
17	Myrtle Beach	South Carolina	United States	29572
18	Dallas	Texas	United States	75246
19	Houston	Texas	United States	77024
20	Salt Lake City	Utah	United States	84112