Cabazitaxel vs Abiraterone or Enzalutamide in Patients With Poor Prognosis Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess and compare the clinical benefit rate in patients with metastatic castrate-resistant prostate cancer and poor prognostic factors treated with cabazitaxel or novel hormonal agents (abiraterone or enzalutamide) as initial therapy, to determine which treatment is most active in this population. Clinical benefit rate is defined as PSA or measurable radiological response of any duration or stable disease for > or equal to 12 weeks, in the absence of other indicators of progression. There is option to cross-over onto the other arm if the patient progresses.

Official Title
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A Phase II, Randomized, Multi-center Study of Cabazitaxel Versus Abiraterone or Enzalutamide in Poor Prognosis-metastatic Castration-resistant Prostate Cancer

Conditions
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Metastatic Castration-Resistant Prostatic Cancer

Intervention / Treatment
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* Drug: cabazitaxel
* Drug: Abiraterone
* Drug: Enzalutamide 160mg daily (oral)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of prostate adenocarcinoma. Able and willing to provide informed consent and to comply with the study procedures Age ≥18 Evidence of metastatic disease on a chest, abdominal, or pelvic CT scan and/or bone scan within 6 weeks of registration Castration resistant disease defined as evidence of radiological and/or PSA progression despite castrate levels of testosterone (serum testosterone < 50 ng/dL (1.7 nmol/L)). For PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals. The first PSA value must be ≥ 2. (Prostate Cancer Working Group 2 (PCWG2) criteria) Poor prognosis disease as defined by any of the following: the presence of liver metastases OR development of castration-resistance within 12 months of orchiectomy or commencement of LHRH antagonist/agonist for metastatic disease OR the presence of 4 or more of the following factors: LDH > ULN ECOG Performance status (PS) 2 visceral metastatic disease serum albumin less than or equal to 4 g/dL ALP > ULN or < 36 months from commencement of initial androgen deprivation therapy to study enrollment ECOG PS 0-2. Adequate end-organ function within 14 days of registration: Haemoglobin ≥ 90 g/L Neutrophils ≥ 1.5 x 109 /L Platelets ≥ 100 x 109/L AST < 1.5 x ULN ALT < 1.5 x ULN Bilirubin ≤ 1.0 x ULN (exceptions for Gilbert's syndrome) Creatinine ≤ 1.5 x ULN At least 21 days have passed since completing radiotherapy (exception for radiotherapy: at least 7 days since completing a single fraction of ≤ 800 cGy to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of randomization. At least 21 days have passed since receiving any investigational agent at the time of registration. At least 21 days have passed since major surgery. Neuropathy ≤ grade 1 at the time of registration. Has recovered from all therapy-related toxicity to ≤ grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) at the time of registration. Eligible for abiraterone acetate and/or enzalutamide as per standard of care practices. Exclusion Criteria: Histologic evidence of small cell/neuroendocrine prostate cancer. Other chemotherapy regimen beyond one prior course of docetaxel. Previously received treatment with cabazitaxel. Received any prior next-generation anti-androgen (e.g. enzalutamide, ARN-509) or CYP 17 inhibitors (e.g. abiraterone, TAK-700). Other condition, illness, psychiatric condition, or laboratory abnormality that may increase the risk associated with administration of cabazitaxel, abiraterone or enzalutamide, study participation, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabazitaxel<br> | Drug: cabazitaxel<br>* Cabazitaxel 25mg/m2 intravenous every 3 weeks until disease progression<br>* Other names: Jevtana;|
| Active Comparator: Abiraterone or enzalutamide<br> | Drug: Abiraterone<br>* Abiraterone 1000mg daily (oral) until disease progression<br>* Other names: Zytiga;Drug: Enzalutamide 160mg daily (oral)<br>* Enzalutamide 160mg daily (oral) until disease progression<br>* Other names: Xtandi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate | To assess and compare the clinical benefit rate in patients with mCRPC and poor prognostic factors treated with cabazitaxel or novel hormonal agents (abiraterone or enzalutamide) as initial therapy, to determine which treatment is most active in this population. Clinical benefit rate is defined as PSA or measurable radiological response of any duration or stable disease for greater than or equal to 12 weeks, in the absence of other indicators of progression. | 12 weeks or more | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of treatment time to progression | To measure the treatment time before any type of progression (symptomatic, PSA, or radiological) between Arm A and Arm B | 12 weeks until disease progression | 
| Progression Free Survival | To measure the progression-free survival of metastatic castration-resistant prostate cancer patients following treatment with cabazitaxel or abiraterone/enzalutamide as initial therapy. | 12 weeks until disease progression | 
| Overall Survival | To measure the overall survival of metastatic castration-resistant prostate cancer patients following treatment with cabazitaxel or abiraterone/enzalutamide as initial therapy. | 12 weeks until 2 years after last study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abiraterone, poor prognosis, castrate-resistant prostate cancer, cabazitaxel, enzalutamide