A Phase 2/3 interventional study of Cabazitaxel and Abiraterone in Prostate Cancer Metastatic and Metastasis, sponsored by The Netherlands Cancer Institute. Completed at 19 sites in Netherlands. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-15.
Sponsored by The Netherlands Cancer Institute · Phase 2/3, Interventional, and Treatment
Rationale:
The aim of this study is to identify the optimal second line treatment option for patients with a poor prognosis metastasized Castration Resistant Prostate Cancer (mCRPC) with respect to Clinical Benefit Rate (CBR) rate and quality of life.
Objective:
The primary endpoint is CBR in mCRPC patients with poor prognostic features and previously treated with docetaxel, randomized between cabazitaxel (Arm A) and novel hormonal agents (abiraterone OR enzalutamide) as second-line therapy (Arm B).
Intervention:
Patients in Arm A will receive cabazitaxel and prednisone and patients in Arm B will receive abiraterone and prednisone OR enzalutamide.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Treatment regimens evaluated in this trial are used in common mCRPC treatment practice and are reimbursed. Risk of side effects or death as a result of treatment is not affected by the trial design. At baseline, prior to each treatment cycle and at end of treatment, patients are requested to visit the out-patient clinic, where a physical exam will be performed in combination with vena puncture for blood analysis. Radiological evaluation will be performed at base line, after 3 months of treatment and at end of treatment. All above mentioned interventions can be considered as standard practice. Patients are requested to fill out QoL and pain/analgesic use questionnaires at base line, prior to each cycle and at end of treatment.
Rationale:
The aim of this study is to identify the optimal second line treatment option for patients with a poor prognosis metastasized Castration Resistant Prostate Cancer (mCRPC) with respect to Clinical Benefit Rate (CBR) rate and quality of life.
Objective:
The primary endpoint is CBR in mCRPC patients with poor prognostic features and previously treated with docetaxel, randomized between cabazitaxel (Arm A) and novel hormonal agents (abiraterone OR enzalutamide) as second-line therapy (Arm B).
Study design:
a prospective, multicenter, national, randomized, open label phase IIB study. Study population: Males over 18 years with mCRPC, previously treated with docetaxel and features of poor prognostic disease; including duration of response to androgen deprivation shorter than one year, liver metastases, disease progression during docetaxel treatment or within 6 months after docetaxel treatment completion.
Intervention:
Patients in Arm A will receive cabazitaxel and prednisone and patients in Arm B will receive abiraterone and prednisone OR enzalutamide.
Main study parameters/endpoints: Primary endpoint: Clinical benefit rate (CBR). Secondary endpoints include: formal comparison of the CBR in both study arms, Time To Symptomatic Progression (TTSP), Time To PSA (prostate specific antigen), Progression (TTPP), and Time To Radiologic Progression (TTRP), progression free survival, overall survival, safety/ toxicity profile and Quality of Life (QoL) and pain response.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Treatment regimens evaluated in this trial are used in common mCRPC treatment practice and are reimbursed. Risk of side effects or death as a result of treatment is not affected by the trial design. At baseline, prior to each treatment cycle and at end of treatment, patients are requested to visit the out-patient clinic, where a physical exam will be performed in combination with vena puncture for blood analysis. Radiological evaluation will be performed at base line, after 3 months of treatment and at end of treatment. All above mentioned interventions can be considered as standard practice. Patients are requested to fill out QoL and pain/analgesic use questionnaires at base line, prior to each cycle and at end of treatment.
Poor prognosis disease as defined by any of the following:
Exclusion Criteria:
Inadequate organ and bone marrow function as evidenced by:
Cabazitaxel 25mg/m2 IV, once every 3 weeks
Drug: Cabazitaxel
At physician's discretion: Abiraterone 1000mg oral, taken daily Prednisone 5mg oral, 2 times a day OR Enzalutamide 160mg oral taken daily
Drug: Abiraterone · Drug: Enzalutamide
Cabazitaxel 25mg/m2 IV, once every 3 weeks
Also known as: No other intervention names
Abiraterone 1000mg oral, taken daily + Prednisone 5mg oral, 2 times a day
Also known as: No other intervention names
Enzalutamide 160mg oral taken daily
Also known as: No other intervention names
Clinical benefit rate
• To assess the Clinical Benefit Rate (CBR) in patients with mCRPC and poor prognostic factors treated with cabazitaxel (Arm A) or novel hormonal agents (abiraterone OR enzalutamide) as second-line therapy (Arm B) who have been treated with docetaxel.
Time frame: From start treatment until 12 weeks of treatment
Comparing clinical benefit rate in arm A and arm B
• To formally compare the Clinical Benefit Rate (CBR) in both study arms A and B.
Time frame: From start treatment until 12 weeks of treatment
Duration of treatment
• To determine duration of treatment (DOT) in mCRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy and for those who cross over to the other study arm as a third-line therapy.
Time frame: for each patient; until end of treatment (for Arm A max 30 weeks, for Arm B max 24 months)
Progression free survival
• To determine the Progression Free Survival (PFS) of mCRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy and for those who cross over to the other study arm as a third-line therapy.
Time frame: for each patient; until progression or through study completion (max 24 months)
Overall survival
• To determine the Overall Survival (OS) of mCRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy.
Time frame: for each patient; until death or end of trial (max 24 months)
(serious) adverse events according to the ctcae v4.03: number of incidents, number of participants with (S)AE's
• To evaluate safety and toxicity profile of cabazitaxel and novel hormone agents (abiraterone OR enzalutamide) as a second line treatment.
Time frame: for each patient: until 28 days after the last treatment
Quality of Life assesed by the FACT-P questionnaire
• Quality of Life (QoL) as assessed by Fundamental Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire in metastatic CRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy.
Time frame: for each patient; until start of the next therapy, death or end of trial (max 24 months)
Quality of Life as assessed by the BPI-S questionnaire
• Quality of Life (QoL) as assessed Brief Pain Inventory-Short form (BPI-S) questionnaire in metastatic CRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy.
Time frame: for each patient; until start of the next therapy, death or end of trial (max 24 months)
Use of pain medication, assessed by a questionnaire about opiate use.
Use of pain medication, assessed by a questionnaire about opiate use in metastatic CRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy.
Time frame: for each patient; until start of the next therapy, death or end of trial (max 24 months)
Time to symptomatic progression
Time To Symptomatic Progression (TTSP) in CRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy and for those who cross over to the other study arm as a third-line therapy.
Time frame: for each patient: until symptomatic progression or through study completion (max 24 months)
Time to PSA progression
Time To PSA Progression (TTPP) in mCRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy and for those who cross over to the other study arm as a third-line therapy.
Time frame: for each patient: until PSA progression or through study completion (max 24 months)
Time to Radiological progression
Time To Radiological Progression (TTRP) in mCRPC patients treated with cabazitaxel or novel hormone agents (abiraterone OR enzalutamide) as second-line therapy and for those who cross over to the other study arm as a third-line therapy.
Time frame: for each patient: until radiological progression or through study completion (max 24 months)
PSA>50% decrease
Rate of PSA\>50% decrease from baseline
Time frame: for each patient; from baseline until end of trial (max 24 months)
Exploratory objectives; neutrophil to lymphocyte ratio
Prostate cancer is a very diverse disease and there is a need for more personalized treatment than offered nowadays. Therefore, three biomarker studies are included in this randomized trial. The value of the neutrophil to lymphocyte ratio will be measured in all patients, to try to find a predictive value
Time frame: For each patient: until the end of treatment, Arm A max 30 weeks, Arm B max 24 months
Exploratory objectives; number of mutations in 73 genes from cell-free DNA
We will draw blood from patients to measure mutations in 73 prostate cancer-related genes out of cell-free DNA. The goal again is to find a predictive value in these DNA mutations and to be able to give more personalized treatment.
Time frame: For each patient: until the end of treatment, Arm A max 30 weeks, Arm B max 24 months
Exploratory objectives; epigenetics-based biomarker discovery using cfDNA
We will isolate chromatinized cfDNA from serum samples of all patients in this trial. Immunoprecipitation will be performed for H3K27ac after which isolated DNA fragments are sequenced, effectively sequencing the enriched functional enhancers that are detected in the serum-derived cfDNA. The aim is to identify distinct functional enhancers that enable outcome prediction.
Time frame: For each patient: until end of treatment (max 24 months)
This study is completed, as verified in Apr 2022. You cannot join it, but the record below documents what was studied.
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The Netherlands Cancer Institute