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Study protocol
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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
Keywords
Clinical Trial Platform; Genetic Biomarker; Prostate Cancer; Precision medicine
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CURRENT STATUS: Published
View the published article at Trials.
Version 2
Posted 18 May, 2020
No community comments so far
Editorial decision: Accept
On 15 Jun, 2020
Reviewer #1 agreed
On 20 May, 2020
Review #1 received
Received 20 May, 2020
Reviewers invited
Invitations sent on 18 May, 2020
Editor assigned
On 14 May, 2020
Submission checks complete
On 13 May, 2020
No comments provided
Review #2 received
Received 22 Apr, 2020
Editorial decision: Major revision
On 22 Apr, 2020
Review #1 received
Received 06 Apr, 2020
Reviewer #2 agreed
On 01 Apr, 2020
Reviewer #1 agreed
On 23 Mar, 2020
Reviewers invited
Invitations sent on 10 Mar, 2020
Editor assigned
On 29 Feb, 2020
Submission checks complete
On 17 Feb, 2020
First submitted
On 12 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
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See the published version of this preprint at Trials.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Study protocol
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Trials.
Version 2
Posted 18 May, 2020
No community comments so far
Editorial decision: Accept
On 15 Jun, 2020
Reviewer #1 agreed
On 20 May, 2020
Review #1 received
Received 20 May, 2020
Reviewers invited
Invitations sent on 18 May, 2020
Editor assigned
On 14 May, 2020
Submission checks complete
On 13 May, 2020
No comments provided
Review #2 received
Received 22 Apr, 2020
Editorial decision: Major revision
On 22 Apr, 2020
Review #1 received
Received 06 Apr, 2020
Reviewer #2 agreed
On 01 Apr, 2020
Reviewer #1 agreed
On 23 Mar, 2020
Reviewers invited
Invitations sent on 10 Mar, 2020
Editor assigned
On 29 Feb, 2020
Submission checks complete
On 17 Feb, 2020
First submitted
On 12 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Trials.
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
This is a list of supplementary files associated with this preprint. Click to download.
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