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

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

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).

Study Overview

• Status: Terminated
• Conditions: Prostatic Neoplasms; Prostate Cancer; Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: cabozantinib; Drug: abiraterone; Drug: prednisone

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
    • Sedona, Arizona, United States, 86336
    • Tucson, Arizona, United States, 85710
  • California
    • Oxnard, California, United States, 93030
    • San Diego, California, United States, 92108
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Aurora, Colorado, United States, 80012
  • Georgia
    • Athens, Georgia, United States, 30607
    • Atlanta, Georgia, United States, 30318
  • Illinois
    • Peoria, Illinois, United States, 61615
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Nevada
    • Las Vegas, Nevada, United States, 89148
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
  • Oregon
    • Tualatin, Oregon, United States, 97062
  • South Carolina
    • Charleston, South Carolina, United States, 29414
    • Greenville, South Carolina, United States, 29605
    • Myrtle Beach, South Carolina, United States, 29572
  • Texas
    • Dallas, Texas, United States, 75246
    • Houston, Texas, United States, 77024
  • Utah
    • Salt Lake City, Utah, United States, 84112

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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: abiraterone acetate; Zytiga(R); 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: abiraterone acetate; Zytiga(R); 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: abiraterone acetate; Zytiga(R); 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: abiraterone acetate; Zytiga(R); Drug: prednisone; Tablets taken orally twice daily

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability as assessed by adverse events	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.	Up to 18 months
Pharmacokinetic Pre-dose Plasma Concentrations of both cabozantinib and abiraterone when administered in combination	When administered in combination, both cabozantinib and abiraterone plasma concentrations will be measured prior to dosing on selected visits	Days 1-4, Week 3, Week 5, Week 7, Week 9, Week 17, and Week 41
Overall survival	Overall survival is defined as the time from randomization to death from any cause.	Up to 36 months
Bone scan response by computer-aided detection (CAD)	Bone scans will be evaluated by an independent radiology facility for response	Up to 18 months
Pharmacokinetic Plasma Area Under the Curve (AUC)	For selected subjects, the plasma AUC of cabozantinib and abiraterone will be measured at Week 5	Week 5

Collaborators and Investigators

• Sponsor: Exelixis

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: November 14, 2013
• First Submitted That Met QC Criteria: November 21, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Estimate): February 20, 2015
• Last Update Submitted That Met QC Criteria: February 19, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: prostate cancer; CRPC; castration resistant prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: XL184-210