Cabazitaxel Versus the Switch to Alternative AR Targeted Therapy Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Primary Resistant Patients to Abiraterone or Enzalutamide
- Conditions
- Prostate Cancer Metastatic
- Interventions
- Registration Number
- NCT02379390
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To demonstrate the superiority in term of radiographic Progression-Free Survival (rPFS) of cabazitaxel at at 25 milligram per meter square (mg/m\^2) plus prednisone (Arm A) versus either enzalutamide at 160 milligram (mg) once daily or abiraterone acetate at 1000 mg once daily plus prednisone (Arm B) in chemotherapy-naïve participants with metastatic Castration-Resistant Prostate Cancer (mCRPC) who have disease progression while receiving androgen receptor (AR) targeted therapy (abiraterone plus prednisone or enzalutamide) within 12 months of treatment initiation (≤12 months).
Secondary Objective:
* To compare efficacy for:
* Prostate-specific antigen (PSA) response rate and Time to PSA progression (TTPP).
* Progression Free Survival (PFS).
* Overall Survival (OS).
* Tumor response rate in participants with measurable disease (RECIST 1.1)
* Pain response and time to pain progression.
* Symptomatic skeletal events (SSE) rate and time to occurrence of any SSE.
* To analyze messenger ribonucleic acids (mRNAs) including androgen-receptor splice variant 7 messenger RNA (AR-V7) as a biomarker in Circulating Tumor Cells (CTCs).
* To evaluate safety in the 2 treatment arms.
- Detailed Description
The duration of the study per participant was approximately 2 years. Each participant was treated until radiographic disease progression, unacceptable toxicity, or participants refusal of further study treatment, and each participant was followed after completion of study treatment until death, study cutoff date, or withdrawal of participant consent.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 8
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Abiraterone acetate or Enzalutamide Ezalutamide Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally once daily along with prednisone 5 mg, orally twice daily from Day 1 to 21 in each treatment cycle (each cycle was of 3 weeks) or enzalutamide 160 mg, orally, until disease progression, unacceptable toxicity, or participant's refusal of further study treatment. Cabazitaxel Cabazitaxel XRP6258 Participants received Cabazitaxel 25 mg/m\^2, intravenously for 1 hour along with prednisone 10 mg orally on Day 1 of every treatment cycle (each cycle was of 3 weeks) until disease progression, unacceptable toxicity, or participant's refusal of further study treatment. Cabazitaxel Prednisone Participants received Cabazitaxel 25 mg/m\^2, intravenously for 1 hour along with prednisone 10 mg orally on Day 1 of every treatment cycle (each cycle was of 3 weeks) until disease progression, unacceptable toxicity, or participant's refusal of further study treatment. Abiraterone acetate or Enzalutamide Abiraterone acetate Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally once daily along with prednisone 5 mg, orally twice daily from Day 1 to 21 in each treatment cycle (each cycle was of 3 weeks) or enzalutamide 160 mg, orally, until disease progression, unacceptable toxicity, or participant's refusal of further study treatment. Abiraterone acetate or Enzalutamide Prednisone Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally once daily along with prednisone 5 mg, orally twice daily from Day 1 to 21 in each treatment cycle (each cycle was of 3 weeks) or enzalutamide 160 mg, orally, until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
- Primary Outcome Measures
Name Time Method Radiographic Progression-Free Survival (rPFS) Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days) rPFS was defined as the time from randomization to the first occurrence of radiological tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or progression of bone lesions using prostate cancer working group 2 (PCWG2) criteria or death due to any cause.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Symptomatic Skeletal Event (SSE) Baseline until the end of study (maximum duration: 1059 days) SSE was the occurrence of a new symptomatic pathological fracture, or the use of external beam radiation to relieve bone pain, or the occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.
Number of Participants With Prostate Specific Antigen (PSA) Response Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days) PSA response was defined as decline of serum PSA from baseline by \>= 50 percent (%).
Time to Occurrence of Any Symptomatic Skeletal Events (SSE) Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days) Time to SSE was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SSE, whichever is earlier.
Duration of Tumor Response Baseline up to disease progression or death due to any cause (maximum duration: 1059 days) Duration of tumor response was defined as the time between the first evaluation at which the tumor response criteria were met and the first documentation of tumor progression.
Pain Response Using Brief Pain Inventory-Short Form (BPI-SF) for Pain Intensity Score Baseline until the end of study (maximum duration: 1059 days) Pain response was analyzed using the brief pain inventory-short form (BPI-SF).
Time to Pain Progression Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days) Time to pain progression was defined as the time interval between the date of randomization and the date of the first documented pain progression.
Overall Survival Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days) Overall Survival was defined as the time interval from the date of randomization to the date of death due to any cause.
Time to PSA Progression Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days) Time to PSA progression was defined as the time interval between the date of randomization and the date of first documented PSA progression as per PCWG2 criteria.
Number of Participants Achieving Tumor Response Baseline up to disease progression or death due to any cause (maximum duration: 1059 days) Tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1.
Progression-free Survival (PFS) Baseline upto progression or death due to any cause (maximum duration: 1059 days) PFS: time interval between date of randomization to first documentation of tumor progression as per RECIST 1.1.
Trial Locations
- Locations (24)
Investigational Site Number 124005
🇨🇦Hamilton, Canada
Investigational Site Number 124002
🇨🇦Montreal, Canada
Investigational Site Number 124009
🇨🇦Quebec, Canada
Investigational Site Number 840024
🇺🇸Anchorage, Alaska, United States
Investigational Site Number 840030
🇺🇸Muscle Shoals, Alabama, United States
Investigational Site Number 840028
🇺🇸Anaheim, California, United States
Investigational Site Number 840004
🇺🇸Sacramento, California, United States
Investigational Site Number 840002
🇺🇸Boca Raton, Florida, United States
Investigational Site Number 840017
🇺🇸Metairie, Louisiana, United States
Investigational Site Number 840027
🇺🇸Lakeland, Florida, United States
Investigational Site Number 840015
🇺🇸Ottawa, Illinois, United States
Investigational Site Number 840006
🇺🇸Port Saint Lucie, Florida, United States
Investigational Site Number 840012
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840026
🇺🇸Omaha, Nebraska, United States
Investigational Site Number 840022
🇺🇸Canton, Ohio, United States
Investigational Site Number 124010
🇨🇦Greenfield Park, Canada
Investigational Site Number 840016
🇺🇸Myrtle Beach, South Carolina, United States
Investigational Site Number 124003
🇨🇦Edmonton, Canada
Investigational Site Number 124006
🇨🇦Montreal, Canada
Investigational Site Number 124004
🇨🇦London, Canada
Investigational Site Number 124007
🇨🇦Ottawa, Canada
Investigational Site Number 124001
🇨🇦Vancouver, Canada
Investigational Site Number 124008
🇨🇦Saskatoon, Canada
Investigational Site Number 840001
🇺🇸Covington, Louisiana, United States