Prostate Cancer Metastatic
Conditions
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.
Interventions
Sponsors
Sanofi
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
* Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma. * Metastatic disease. * Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate or enzalutamide within 12 months of treatment initiation (≤12 months) by at least one of the following: * Progression in measurable disease Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG2). * Rising PSA defined (PCWG2) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. * A PSA value of at least 2 nanogram/milliliter (ng/mL) is required at study entry. * Effective castration (serum testosterone levels ≤0.5 ng/mL). * Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment. * Signed written informed consent.
Exclusion criteria
* Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed \>3 years ago. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion. Prior docetaxel in hormone sensitive setting is allowed if completed \>1 year before randomization. Prior immunotherapy is allowed. * Less than 28 days elapsed from prior treatment with immunotherapy, radiotherapy, or surgery to the time of randomization. * Adverse events (excluding alopecia and those listed in the specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 (%). |
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Study conducted at 6 active centers in United States and Canada. A total of 8 participants were enrolled between 17 June 2015 to 13 Mar 2016. Total 15 participants were screened, out of which 7 were screen failures and 8 were randomized and treated in the study. Study was terminated early due to very low recruitment rate in both countries involved.
Pre-assignment details
Participants were randomized to receive either chemotherapy (cabazitaxel) or antiandrogen receptor targeted therapy (abiraterone or enzalutamide were assigned based on previous Androgen receptor \[AR\] targeted treatment in which participants previously treated with abiraterone were treated with enzalutamide and vice versa due to resistance).
Participants by arm
| Arm | Count |
|---|---|
| Cabazitaxel Participants received Cabazitaxel 25 mg/m\^2, intravenously for 1 hour on Day 1 of each cycle (each cycle was of 3 weeks), plus prednisone 10 mg orally given daily until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment. | 4 |
| Abiraterone Acetate or Enzalutamide Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally continuously 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 continuously once daily from Day 1 to Day 21 in each treatment cycle (each cycle was of 3 weeks), until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment. | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Investigator's decision | 1 | 0 |
| Overall Study | Study Termination | 0 | 1 |
Baseline characteristics
| Characteristic | Cabazitaxel | Abiraterone Acetate or Enzalutamide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 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 / 4 | 0 / 4 | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 3 / 4 | 2 / 4 | 1 / 1 | 1 / 3 |
| serious Total, serious adverse events | 1 / 4 | 2 / 4 | 0 / 1 | 2 / 3 |
Outcome results
Primary
Radiographic Progression-Free Survival (rPFS)
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.
Time frame: Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Duration of Tumor Response
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.
Time frame: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Number of Participants Achieving Tumor Response
Tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1.
Time frame: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Number of Participants With Prostate Specific Antigen (PSA) Response
PSA response was defined as decline of serum PSA from baseline by \>= 50 percent (%).
Time frame: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Overall Survival
Overall Survival was defined as the time interval from the date of randomization to the date of death due to any cause.
Time frame: Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Pain Response Using Brief Pain Inventory-Short Form (BPI-SF) for Pain Intensity Score
Pain response was analyzed using the brief pain inventory-short form (BPI-SF).
Time frame: Baseline until the end of study (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Percentage of Participants With Symptomatic Skeletal Event (SSE)
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.
Time frame: Baseline until the end of study (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Progression-free Survival (PFS)
PFS: time interval between date of randomization to first documentation of tumor progression as per RECIST 1.1.
Time frame: Baseline upto progression or death due to any cause (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Time to Occurrence of Any Symptomatic Skeletal Events (SSE)
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.
Time frame: Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Time to Pain Progression
Time to pain progression was defined as the time interval between the date of randomization and the date of the first documented pain progression.
Time frame: Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.
Secondary
Time to PSA Progression
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.
Time frame: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
Population: Planned analysis could not be performed due to early study termination.