A randomized, open label, Phase IIB trial of Optimal Sequencing of Treatment Options for Poor Risk Metastasized Castration Resistant Prostate Cancer Previously Treated with Docetaxel (OSTRICh trial)

INTERVENTION: CONDITION: ; metastasized castration resistant ; Prostate cancer 10036958 10038597 INCLUSION CRITERIA: 1. Histological diagnosis of prostate adenocarcinoma., 2. Able and willing to provide informed consent and to comply with the study procedures, 3. Age *18, 4. Evidence of bone, visceral and/or lymph node metastases on bone scan, CT‐scan or MRI., 5. Must have received at least one prior regimen of docetaxel treatment for at least 12 weeks (four courses) and no other prostate cancer treatments between docetaxel and randomization, other than prednisone., 6. Continued androgen deprivation therapy either by LHRH agonist/ antagonist or orchiectomy., 7. Treatment with curative intent is not an option and patient has an indication for systemic treatment as judged by the medical care provider, 8. Evidence of progressive metastatic disease by PSA progression (Prostate Cancer Working Group 3 (PCWG3) criteria: at least 2 rises at a minimum of 1‐week intervals. The first PSA value must be * 2 ng/ml) and/or radiological progressi PRIMARY OUTCOME: Primary endpoint: ; ; To establish the Clinical Benefit Rate (CBR) in both study arms: ; ; Percentage of patients that fulfill the criteria of clinical benefit. Patients ; are considered to have had a clinical benefit if they have a radiological ; response of any duration or stable disease for * 12 weeks, in the absence of ; symptomatic progression, or objective disease progression. ; ; Radiological Response ; Subjects that have measurable disease at screening will be evaluated for ; response on the basis of RECIST criteria v1.1, Tumor measurements using ; physical examination, chest, abdomen, pelvic CT scan, and/or MRI or other ; appropriate techniques deemed suitable by the investigator will be performed at ; screening within 28 days of subject registration and repeated at week 6, 12, 18 ; and 24 followed by every 12 weeks. ; ; Symptomatic or objective disease Progression ; Disease Progression is defined as the development of symptomatic or ; radiological progression at any time. Progression will be classified as any of ; the following: ; 1. Symptomatic progression: worsening of cancer‐related symptoms mandating a ; stop of all treatments, a change in anti‐cancer therapy (radiation, ; chemotherapy or antihormonal therapy), or * 2 level decrease in WHO PS or death ; of any cause. Radiotherapy does not account for symptomatic progression when ; administered in the first 4 weeks of this study. ; 2. Radiological progression: RECIST criteria v1.1 for measurable disease and/or ; appearance of * 2 new bone lesions on whole body bone scan confirmed on a ; subsequent scan. All radiological images will be assessed by an independent ; radiologist for central review of the RECIST criteria.; SECONDARY OUTCOME: Secondary endpoints: ; 1. Formal comparison of the CBR in both study arms. ; 2. Rate of PSA >50% decrease from baseline ; 3. Duration of treatment; time from randomization to last day of treatment. ; ; All time to event endpoints are met at death and censored at last follow‐up; ; 4. Time To Symptomatic Progression TTSP;time from randomization to day of ; worsening of cancer‐related symptoms mandating a stop of all treatments, a ; change in anti‐cancer therapy (radiation, chemotherapy or antihormonal therapy) ; or * 2 level decrease in WHO PS. Radiotherapy does not account for symptomatic ; progression when administered in the first 4 weeks of this study. ; 5. Time To Radiological Progression (TTRP); time from randomization to day of ; radiological progression: RECIST criteria v1.1 for measurable disease or ; appearance of * 2 new bone lesions on whole body bone scan confirmed on a ; subsequent scan. ; 6. Time To PSA Progression (TTPP); time from randomization to PSA progression ; (PCWG3 criteria: at least 2 rises at a minimum of 1‐week intervals. The first ; PSA value must be * 2 ng/ml). ; 7. Progression Free Survival (PFS); time from randomization to the first date ; of progression on study medication as measured by PSA progrression (PCWG3 ; criteria), tumor progression (RECIST 1.1 criteria and PCWG3 criteria), ; symptomatic progression; stop of all treatments, a change in anti‐cancer ; therapy (radiotherapy, chemotherapy or antihomonal therapy), >2 level decrease ; in WHO PS or death of any cause. Radiotherapy does not account for symptomatic ; progression when administered in the first 4 weeks of this study. PFS ; isassessed in patients who are treated with either arms as second line ; treatment and in patients who crossed over to the other treatment arm. ; 8. Overall Survival; time from randomization to date of death. Follow up will ; be maximum 3 years. ; 9. To evaluate safety and toxicity profile of cabazitaxel and novel hormone ; agents (abiraterone OR enzalutamide) all Adverse Events (AEs; assessed by CTCAE ; 4.03 grading) and Serious Adverse Events (SAEs) will be recorded during second ; line cabazitaxel/abiraterone OR enzalutamide treatment. ; 10. Quality of Life (QoL) as assessed by FACT‐P questionnaire and Pain response ; as assessed by BPI‐S questionnaire and opiate use will be recorded during ; second line cabazitaxel/abiraterone OR enzalutamide treatment ;