Castration Resistant Prostate Cancer, Prostate Cancer, Prostatic Neoplasms
Conditions
Keywords
CRPC, castration resistant prostate cancer, prostate cancer
Brief summary
This study was conducted in subjects in chemotherapy-naïve subjects with bone-metastatic castration-resistant prostate cancer (CRPC).
Detailed 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.
Interventions
DRUGcabozantinib
DRUGabiraterone
DRUGprednisone
Sponsors
Exelixis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression Free Survival (PFS) | Up to 18 Months | PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause, as assessed by Independent Radiology Committee (IRC). The sponsor terminated the study early due to business reasons. As such, no data were collected for efficacy analyses. |
Countries
United States
Participant flow
Recruitment details
This study enrolled subjects from 11 February 2014 (first patient enrolled) through 02 September 2014 (Sponsor decision to end study). The study was terminated prior to completing enrollment due to Sponsor decision (not based on any safety results).
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 - Cabozantinib 40 mg, po QD + Abiraterone Cabozantinib 40 mg, po QD + abiraterone with prednisone | 14 |
| Arm 2 - Cabozantinib 20 mg, po QD + Abiraterone Cabozantinib 20 mg, po QD + abiraterone with prednisone | 13 |
| Arm 3 - Cabozantinib 20 mg, po QOD + Abiraterone Cabozantinib 20 mg, po QOD + abiraterone with prednisone | 13 |
| Arm 4 - Abiraterone Only Abiraterone with prednisone only | 14 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | No Treatment Given | 0 | 0 | 0 | 1 |
| Overall Study | Progressive Disease | 0 | 1 | 1 | 1 |
| Overall Study | Sponsor Decision to terminate study | 14 | 12 | 12 | 10 |
Baseline characteristics
| Characteristic | Arm 2 - Cabozantinib 20 mg, po QD + Abiraterone | Arm 3 - Cabozantinib 20 mg, po QOD + Abiraterone | Arm 4 - Abiraterone Only | Arm 1 - Cabozantinib 40 mg, po QD + Abiraterone | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 10 Participants | 11 Participants | 12 Participants | 44 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 10 Participants |
| Age, Continuous | 74 years | 73 years | 70 years | 76 years | 73 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 13 Participants | 14 Participants | 13 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 12 Participants | 13 Participants | 45 Participants |
| Region of Enrollment United States | 13 participants | 13 participants | 14 participants | 14 participants | 54 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 14 Participants | 14 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 1 / 14 | 0 / 12 | 1 / 13 |
| other Total, other adverse events | 13 / 14 | 10 / 14 | 11 / 12 | 11 / 13 |
| serious Total, serious adverse events | 2 / 14 | 4 / 14 | 1 / 12 | 1 / 13 |
Outcome results
Primary
Radiographic Progression Free Survival (PFS)
PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause, as assessed by Independent Radiology Committee (IRC). The sponsor terminated the study early due to business reasons. As such, no data were collected for efficacy analyses.
Time frame: Up to 18 Months
Population: As pre-specified in the protocol, a total of 140 PFS events were required for this analysis; given that only 54 participants were enrolled and the study terminated early after 9 months, no data were collected or analyzed as planned for this outcome measure.