ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer

Sponsor
Karolinska Institutet
Study ID
NCT03903835
Phase
PHASE3
Status
Recruiting
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Conditions

  • Metastatic Castration-resistant Prostate Cancer (mCRPC)
  • Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Eligibility Criteria

Sex
MALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Enzalutamide Oral Capsule — DRUG
    Detailed 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 — DRUG
    Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.
  • Carboplatin — DRUG
    Carboplatin 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 — DRUG
    Detailed 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 — DRUG
    Detailed 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 — DRUG
    Detailed 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 — DRUG
    Niraparib 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 — DRUG
    Capivasertib 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 — DRUG
    Detailed 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 — DRUG
    Detailed 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).

Study Details

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.

Key Dates

Start date
Feb 1, 2019
Status verified
Apr 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
750 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Control: Standard Care
    Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
  • Experimental: Treatment 1 in mHSPC: AR signalling inhibitors (ARSi)
    Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
  • Experimental: Treatment 2 in mHSPC: taxane-based chemotherapy in combination with ARSi
    Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi.
  • Experimental: Treatment 3 in mHSPC: Poly ADP Ribose Polymerase (PARP) inhibitor
    DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.
  • Experimental: Treatment 1 in mCRPC: AR signalling inhibitors (ARSi)
    Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
  • Experimental: Treatment 2 in mCRPC: Poly ADP Ribose Polymerase (PARP) inhibitor
    DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.
  • Experimental: Treatment 3 in mCRPC: selective AKT Inhibitor
    Patients with alterations in the PI3K pathway will have an increased chance of receiving the combination treatment with Capivasertib plus Docetaxel.
  • Experimental: Treatment 4 in mCRPC: Carboplatin
    Only patients with DNA-repair deficiency will be treated with Carboplatin as second line treatment in the castration-resistant phase of ProBio.

Primary Outcome Measure

Progression free survival (PFS) in mCRPC [ Time Frame: Until progressive disease or 60 months from start of treatment, whatever occurs first. ]

Central Contacts

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