The ProBio Trial: Molecular Biomarkers for Advancing Personalized Treatment Decision in Patients with Metastatic Castration-Resistant Prostate Cancer
Background: 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 tumour 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.
Methods: 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.
Discussion: 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.
Conclusions: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.
Trial registration:
ClinicalTrials.gov Identifier: NCT03903835
Date of registration: April 4, 2019
URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03903835
Status: Recruiting
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Posted 18 May, 2020
On 26 Jun, 2020
On 15 Jun, 2020
On 20 May, 2020
Received 20 May, 2020
Invitations sent on 18 May, 2020
On 14 May, 2020
On 13 May, 2020
Received 22 Apr, 2020
On 22 Apr, 2020
Received 06 Apr, 2020
On 01 Apr, 2020
On 23 Mar, 2020
Invitations sent on 10 Mar, 2020
On 29 Feb, 2020
On 17 Feb, 2020
On 12 Feb, 2020
The ProBio Trial: Molecular Biomarkers for Advancing Personalized Treatment Decision in Patients with Metastatic Castration-Resistant Prostate Cancer
Posted 18 May, 2020
On 26 Jun, 2020
On 15 Jun, 2020
On 20 May, 2020
Received 20 May, 2020
Invitations sent on 18 May, 2020
On 14 May, 2020
On 13 May, 2020
Received 22 Apr, 2020
On 22 Apr, 2020
Received 06 Apr, 2020
On 01 Apr, 2020
On 23 Mar, 2020
Invitations sent on 10 Mar, 2020
On 29 Feb, 2020
On 17 Feb, 2020
On 12 Feb, 2020
Background: 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 tumour 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.
Methods: 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.
Discussion: 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.
Conclusions: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.
Trial registration:
ClinicalTrials.gov Identifier: NCT03903835
Date of registration: April 4, 2019
URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03903835
Status: Recruiting
Figure 1
Figure 2
Figure 3