ProBio is an international, outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic prostate cancer. Patients will be randomized to control or experimental treatment arms. Patients in the control arm will receive standard of care following national guidelines. Patients in the experimental arm will be randomized to treatments based on a biomarker signature inferred from diagnostic tissue or liquid biopsy profiling. The predefined biomarker signatures are tumor properties or mutations in genes/pathways with previously demonstrated clinical validity (e.g. prognostic value or association with treatment response). The biomarker signatures are identified using a hybridisation capture gene panel specifically designed for prostate cancer.
Man with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing newly diagnosed (i.e. de novo) hormone sensitive prostate cancer (mHSPC) or first-line castration resistant prostate cancer (mCRPC)
Distant metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI
Adequate health as assessed by the investigator to receive all available treatments in the trial
ECOG/WHO (Eastern Cooperative Oncology Group/ World Health Organization) performance score 0-2
Other malignancies within 5 years except non-melanoma skin cancer
Within 6 months of randomization: myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, TIA (transient ischemic attack), or congestive heart failure NYHA (New York Heart Association) class III or IV
Uncontrolled hypertension
Uncontrolled hypotension
Sequential
Enzalutamide Oral Capsule
DrugDetailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).
Abiraterone Oral Tablet
DrugDetailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.
Carboplatin
DrugCarboplatin will be administered every 3rd week with an AUC (area under curve) = 5 with a dose calculated according to the Carboplatin AUC Dose calculation (Calvert formula):Dose (mg) = TargetAUC (mg/ml x min) x \[GFR ml/min + 25\].
Cabazitaxel 60 mg Solution for Injection
DrugDetailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.
Docetaxel Injectable Solution
DrugDetailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.
Radium Chloride Ra-223
DrugDetailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.
Niraparib plus Abiraterone acetate plus Prednisone
DrugNiraparib and Abiraterone acetate will be provided by Janssen and will be provided either as a fixed dose combination or as single agents. Detailed use of the study treatment including dose and dosages are described in the Investigator's brochures and SmPC.
Capivasertib plus Docetaxel
DrugCapivasertib is provided by AstraZeneca and will be given in combination with Docetaxel. All subjects will be given up to ten 21-day docetaxel cycles. All subjects will receive Capivasertib, which will be administered as tablets taken twice a day orally, on a 4 days on/3 days off continuous schedule, commencing cycle one, day 2, until disease progression.
Apalutamide
DrugDetailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).
Darolutamide
DrugDetailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).
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Treatment groupsSee each treatment group below.
Progression free survival (PFS) in mCRPC
Progression will be evaluated by the established international standards of the Prostate Cancer Working Group version 3 (PCWG3) and for soft tissue metastases (e.g. lung, liver and lymph nodes) according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1).
Progression free survival (PFS) in mHSPC
Time to development of castration-resistance, as defined by EAU guidelines (biochemical progression or radiologic progression)
Treatment response rate in mCRPC
Treatment response is evaluated according to PCWG3 and RECIST 1.1
Overall survival (OS)
OS is defined as time to death from any cause (overall and prostate cancer specific)
Patient Reported Outcome Measures (PROM)
QoL will be assessed using the EORTC QLQ-C30 instrument
Cost-effectiveness
Cost effectiveness will be assessed by using the EQ-5D-5L instrument to estimate health utilities. Treatment costs will be based on drug costs and reimbursement data.
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Karolinska Institutet
Lead sponsor
The Swedish Research Council
Collaborator
Kom Op Tegen Kanker
Collaborator
Janssen Pharmaceutica N.V., Belgium
Collaborator
AstraZeneca
Collaborator
Cancerfonden
Collaborator
