Sentinel™ Trial: A Prospective Study Evaluating the Performance and Clinical Benefit of Personalized ctDNA-based MRD Testing to Detect Recurrence and Monitor Treatment Response in Patients With Solid Tumors

Study Overview
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Brief Summary
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The Sentinel™ Trial is a non-randomized, large-scale observational trial designed to: 1) evaluate the ability of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) testing to detect recurrence in advance of standard-of-care techniques across solid tumors, and 2) determine the clinical benefit of therapy in ctDNA-positive participants. The study offers the opportunity to 1) serially monitor participants for ctDNA changes, 2) define ctDNA kinetics across tumor and therapy types, 3) identify participants with ctDNA evidence of MRD, and 4) understand the clinical benefit of ctDNA status on treatment outcomes.

Detailed Description
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Patients with a confirmed diagnosis of a stage I through III solid tumor who have had definitive therapy or curative surgery within the last 5 years or are planning curative surgery may be eligible for the Sentinel Trial. Patients must have a surplus formalin-fixed paraffin-embedded tumor specimen available at screening, or a planned resection within 28 days of screening. To support ctDNA assessment, study procedures will be limited to serial blood draws repeated every 12 weeks until investigator determined recurrence. Upon recurrence, participants will remain on study for 3 years in survival follow-up.

Official Title
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Sentinel™ Trial: A Prospective Study Evaluating the Performance and Clinical Benefit of Personalized ctDNA-based MRD Testing to Detect Recurrence and Monitor Treatment Response in Patients With Solid Tumors

Conditions
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Cancer

Participation Criteria
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Eligibility Criteria
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Study participants must meet all the inclusion criteria below to enroll: Male or female participants ≥ 18 years of age; Confirmed diagnosis of a stage 1-3 solid tumor; Curative surgery or definitive therapy (e.g., chemoradiation, stereotactic body radiation therapy [SBRT]) completed <5 years ago without any current evidence of radiographical or biochemical recurrence, or planned within 28 days of consent; Surplus formalin fixed paraffin embedded tumor specimen available; Able to tolerate venipuncture for blood draws; Primary diagnosis is not glioma or CNS disease; Both the tumor tissue sample and blood sample pass the quantity and quality parameters to allow for a successful MRD test result.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity | Evaluate ability of ctDNA-based MRD monitoring to detect disease recurrence in advance of SOC recurrence monitoring across solid tumors, as stratified by tumor type and adjuvant therapy status. With sensitivity being the proportion of participants with radiographic recurrence who first had a ctDNA recurrence and specificity being the proportion of participants without radiographic recurrence who did not first have a ctDNA recurrence. | 8 years | 
| ctDNA Response Rate | Determine the clinical benefit of treatment in ctDNA-positive participants, as stratified by therapy class (targeted, immuno-, chemo-, etc.), individual therapy, tumor type, stage, and biomarker status. With ctDNA response rate being the proportion of participants with >50% reduction in mean variant allele frequency (VAF) on-treatment at 3 months compared to baseline VAF. | 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS): Duration of time between initiation of treatment and radiographic recurrence (investigator assessment) or death | Determine the relationship between ctDNA response, clearance, and kinetics and radiographically determined disease-free survival and overall survival overall and as stratified by therapy class (targeted, immuno-, chemo-, etc.), individual therapy, tumor type, stage, and biomarker status. | 8 years | 
| Disease Free Survival (DFS): Duration of time between initiation of treatment and radiographic recurrence (investigator assessment) or death | Determine the clinical benefit of therapy versus surveillance in ctDNA-positive participants as stratified by therapy class (targeted, immuno-, chemo-, etc.), individual therapy, tumor type, and biomarker status (DFS, OS). With Disease Free Survival (DFS) being the duration of time between initiation of treatment and radiographic recurrence (investigator assessment) or death and Overall survival (OS) being the duration of time between initiation of treatment and death. | 8 years | 
| Disease Free Survival (DFS): Duration of time between initiation of treatment and radiographic recurrence (investigator assessment) or death | Determine the adjuvant therapy utilization rate stratified by ctDNA status, tumor type and tumor stage. | 8 years |