Combo of Cabozantinib With Abiraterone in Chemotherapy-Naïve Subjects With Bone-Metastatic CRPC

Exelixis

Status and phase: Terminated; Phase 2

Conditions: Prostatic Neoplasms; Prostate Cancer; Castration Resistant Prostate Cancer

Treatments: Drug: cabozantinib; Drug: prednisone; Drug: abiraterone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01995058

XL184-210

Details and patient eligibility

About

This study was conducted in subjects in chemotherapy-naïve subjects with bone-metastatic castration-resistant prostate cancer (CRPC).

Full description

The goal of this clinical trial was to learn if the combination of the drugs cabozantinib and abiraterone works for men that were chemotherapy-naive, bone metastasis CRPC patients. It was designed to learn about the safety of cabozantinib. The main questions are:

1. Does it work and is it safe in men with chemotherapy-naïve bone- metastatic castration resistant CRPC?
2. What was the clinical benefit at different dose levels of the combination of abiraterone and cabozantinib in this patient population?

Participants were assigned to one of the four treatment groups:

Arm 1. cabozantinib at a dose of 40 mg every day (QD) plus abiraterone with prednisone; Arm 2. cabozantinib at a dose of 20 mg QD plus abiraterone with prednisone; Arm 3. cabozantinib at a dose of 20 mg every other day (QOD) plus abiraterone with prednisone; Arm 4. abiraterone with prednisone.

Enrollment: 54 patients

Sex: Male

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 4 patient groups

Arm 1: Cabozantinib 40 mg + abiraterone with prednisone

Experimental group

Description:

Cabozantinib 40 mg, by mouth daily (po QD), + abiraterone with prednisone

Treatment:

Drug: abiraterone

Drug: prednisone

Drug: cabozantinib

Arm 2: Cabozantinib 20 mg + abiraterone and prednisone

Experimental group

Description:

Cabozantinib 20 mg, by mouth daily (po QD), + abiraterone with prednisone

Treatment:

Drug: abiraterone

Drug: prednisone

Drug: cabozantinib

Arm 3: Cabozantinib 20 mg (every other day) + abiraterone and prednisone

Experimental group

Description:

Cabozantinib 20 mg every other day with abiraterone and prednisone

Treatment:

Drug: abiraterone

Drug: prednisone

Drug: cabozantinib

Arm 4: Abiraterone and prednisone only

Active Comparator group

Description:

Abiraterone with prednisone

Treatment:

Drug: abiraterone

Drug: prednisone