The ProBio trial: molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer.

The ProBio trial: molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer.

Publication date: Jun 26, 2020

Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis.

The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC.

Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study.

The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.

ClinicalTrials.gov Identifier NCT03903835. Date of registration: April 4, 2019. Status: Recruiting.

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Concepts Keywords
Biomarker Tumor
Biomarkers Clinical medicine
Castration Biomarkers
Control Arm Branches of biology
Germline MCRPC
Heterogeneity Prostate cancer
Metastatic Prostvac
Physician Cancer biomarker
Probability
Prostate
Prostate Cancer
Randomization
Sequencing
Tumor

Semantics

Type Source Name
disease MESH prostate cancer
pathway KEGG Prostate cancer
disease MESH tumor
disease MESH men
pathway REACTOME Reproduction
drug DRUGBANK Trestolone
disease MESH death
drug DRUGBANK Acetate ion
drug DRUGBANK Enzalutamide
drug DRUGBANK Cabazitaxel
disease MESH biopsy
disease MESH varia
drug DRUGBANK Carboplatin
drug DRUGBANK Docetaxel
drug DRUGBANK Platinum
disease MESH defects
disease MESH microsatellite instability
disease MESH adenocarcinoma

Original Article

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