Patients with metastatic hormone-sensitive and castration-resistant prostate cancer MedDRA version: 21.1 Level: PT Classification code 10071119 Term: Hormone-dependent prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Abiraterone (Zytiga)
Product Name: Zytiga
Product Code: L02BX03
Pharmaceutical Form: Tablet
Trade Name: Enzalutamide (Xtandi)
Pharmaceutical Form: Capsule, soft
Trade Name: Cabazitaxel (
Sponsors
Karolinska Institutet
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Male patients, aged above 18 years, with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing: 1. Newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) or 2. First-line mCRPC (i.e. first evidence of progressive metastatic prostate cancer under castrate levels (=65 years) yes F.1.3.1 Number of subjects for this age range 1600
Exclusion criteria
Exclusion criteria: • The determination of a biomarker signature is necessary to randomise patients during ProBio. Patients with mCRPC with undetectable levels of ctDNA will therefore be excluded. In case of de novo mHSPC, failure to detect ctDNA or somatic alterations from the primary tumour biopsies will exclude the patient from the trial • Other malignancies within 5 years except non-melanoma skin cancer • Within 6 months of randomization: myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, TIA, or congestive heart failure NYHA class III or IV • Uncontrolled hypertension: SBP > 160 mmHg and or DBP > 95 mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment 4. Uncontrolled hypotension: SBP < 90 mmHg and/or DBP < 50 mmHg • Upon entering the mHSPC phase of the trial, prior systemic therapy (including ADT) is not allowed. Patients with mCRPC may not enter the trial when they have already received prior systemic therapy (with the exception of standard ADT) for mCRPC. • Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretationof study results. This includes a medical history significant forarrhythmia (e.g. multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted to enter the study. • Unable to comply with study procedures • Current participation in another clinical trial that will be in conflict with the present study, administration of an investigational therapeutic or invasive surgical procedure within 28 days prior to study enrolment • Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the Investigator to be unlikely to complete the study • Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study • Any medical condition that would make use of the study treatments contraindicated, according to the SmPC, e.g. significant heart or liver disease. The investigator should check the SmPC and/or IB for the assigned study treatments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment class choice based on a biomarker signature can improve PFS compared to standard of care in male patients with mHSPC and mCRPC, where standard of care is defined as clinician-patient treatment decision without access to information on the biomarker profile. Progression free survival (PFS) is defined according to disease stage at trial entry, using: • For mHSPC: Time to development of castration-resistance (EAU guidelines) • For mCRPC: Time to no longer clinical benefit (NLCB), Prostate Cancer Working Group (PCWG3 guidelines);Secondary Objective: To determine whether treatment class choices based on a biomarker signature can: • improve PSA-PFS • improve radiographic PFS • improve treatment response rate (RR) after 3-4 months of treatment • improve PFS2, defined as the time from the initial study randomisation to the 2nd progression or death from any cause • improve overall survival, defined as the time from the initial study randomisation to death from any cause • improve quality of life • improve health economy • does not increase toxicity (i.e. drug safety) • To identify additional predictive and prognostic biomarkers • Identify a certain treatment class that is superior for a certain XML File Identifier: 2dRTZRX5xH6eaYtAkMdzXZdqcAw= Page 48/64 biomarker signature compared to other treatment classes (efficacy) • Identify superior treatment sequencing regimens (i.e. is treatment A followed by treatment B superior to treatment B followed by treatment A given a biomarker signature);Primary end point(s): Progression free survival (PFS) (defined according to disease stage at trial entry: for metastatic hormone sensitive prostate cancer: Time to development of castration-resistance (EAU guidelines) for metastatic castration resistant prostate cancer: Time to no longer clinical benefit (NLCB), Prostate Cancer Working Group (PCWG3 guidelines);Timepoint(s) of evaluation of this end point: for mHSPC: at each study follow up visi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: Treatment class response rate at 3-4 months in mCRPC, where treatment response is evaluated according to PCWG3 and RECIST 1.1, and time to death (overall survival). Treatment response rate at 6 months on treatment (mHSPC) Quality of life: Quality of life will be assessed using EQ-5D-5L, EORTC QLQ-C30 and BPI-SF. 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. Safety endpoints: Frequency and severity of adverse events will be evaluated. ? To identify additional predictive and prognostic biomarkers ? Identify a certain therapy class that is superior for a certain biomarker signature compared to other therapy classes (efficacy) ? Identify superior treatment sequencing regimens (i.e. is treatment A followed by treatment B superior to treatment B followed by treatment A given a biomarker signature) Exploratory objectives: the following exploratory objectives will be addressed: ? Can ctDNA fraction dynamics replace radiographic and biochemical response evaluation for therapy response assessment? ? Retrospective analysis of the gene panel profile to identify new biomarker signature- treatment associations. ? Analysis of cell-free DNA methylomes ? Analysis of cell-free RNA ? RNA Analysis of thrombocytes ? Prospective DNA analysis of CTCs ? RNA analysis of CTCs ? cfRNA and cfDNA analysis of urine ? Prospective evaluation of clinical validity of PSMA-PET/CT-scan in 1st line mCRPC (CUTR-01 observational cohort study, PI: B. Sautois, CHU Liège, Belgium) ? Development of a new patient-reported outcome measure (PROM) instrument to evaluate the quality-of-life (QoL) of patients with advanced prostate cancer ? Quantitative analysis of androgen receptor perturbations using a blood-based liquid biopsy as a treatment-predictive biomarker for men with metastatic castration- resistant prostate cancer. ? Patient derived o | — |
Countries
Belgium, Norway, Sweden, Switzerland
Contacts
Public ContactMedical Epidemiology & Biostat.
Karolinska Institute
Outcome results
None listed