Establishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal Cancer

Study Overview
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Brief Summary
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This study measures the levels of circulating tumor DNA (ctDNA) in patients with stage II-III rectal cancer before, during, and after treatment to find out if the presence or absence of ctDNA in patient's blood using the Signatera test can be used to gauge how different treatments may affect rectal cancer. ctDNA is DNA from the rectal cancer that is circulating in the blood. The purpose of this study is to understand if the way rectal tumors respond to standard treatment can be associated with varying levels of ctDNA.

Detailed Description
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PRIMARY OBJECTIVE: I. To estimate the percentage of participants that achieve complete clinical response. SECONDARY OBJECTIVES: I. To assess circulating tumor deoxyribonucleic acid (ctDNA) status among participants receiving total neoadjuvant therapy (TNT). II. To assess molecular residual disease (MRD i.e., ctDNA status). III. To assess the rate of transabdominal surgery. IV. To assess the rate pathological complete response after surgery. V. To assess the rate of watch and -wait (W&W) after TNT. VI. To assess disease-free survival (DFS). VII. To assess overall survival (OS). EXPLORATORY OBJECTIVES: I. To characterize ctDNA clearance or non-clearance patterns during TNT. II. To correlate ctDNA levels with a participant's pathological features. III. To preliminary assess the prognostic performance of ctDNA levels in relation to participant's clinical outcome. OUTLINE: Patients undergo collection of blood samples at baseline (before any neoadjuvant therapy), every 2 months while undergoing TNT, and then every 3 months for up to 3 years after completion of TNT. Patients' medical records are also reviewed. Patients may undergo collection of tissue sample if an archival tissue sample is not available.

Official Title
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Establishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal Cancer

Conditions
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Rectal Adenocarcinoma, Stage II Rectal Cancer AJCC v8, Stage IIA Rectal Cancer AJCC v8, Stage IIB Rectal Cancer AJCC v8, Stage IIC Rectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IIIA Rectal Cancer AJCC v8, Stage IIIB Rectal Cancer AJCC v8, Stage IIIC Rectal Cancer AJCC v8

Intervention / Treatment
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* Procedure: Biopsy
* Procedure: Biospecimen Collection
* Other: Electronic Health Record Review


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must provide written informed consent before any study-specific procedures or interventions are performed Participants aged >= 18 years Pathologically-confirmed stage II or III primary adenocarcinoma of the rectum: T3N0M0 - T4bN2M0 Exclusion Criteria: Has radiologic evidence of distant metastases at the time of screening/enrollment Has received prior treatment for their rectal adenocarcinoma Requires or has received blood transfusion within 1 month of study enrollment

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (biospecimen collection, medical record review)<br>Patients undergo collection of blood samples at baseline (before any neoadjuvant therapy), every 2 months while undergoing TNT, and then every 3 months for up to 3 years after completion of TNT. Patients' medical records are also reviewed. Patients may undergo collection of tissue sample if an archival tissue sample is not available. | Procedure: Biopsy<br>* Undergo biopsy<br>* Other names: Bx;Procedure: Biospecimen Collection<br>* Undergo collection of blood and/or tissue samples<br>* Other names: Biological Sample Collection;Other: Electronic Health Record Review<br>* Medical records are reviewed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical response (cCR) | cCR following TNT will be analyzed using the TNT analysis set. Proportions of participants that achieved cCR will be calculated and the exact 95% confidence interval (CI) will be presented. | From time of treatment start up to date of completing total neoadjuvant therapy (TNT), up to 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive circulating tumor deoxyribonucleic acid (ctDNA) | The proportion of ctDNA positive participants (at baseline, throughout TNT, and follow-up) and its exact 95% CI will be evaluated using the ctDNA analysis set. Where appropriate, sub-analyses will be conducted using populations that underwent surgery or were monitored using a watch and wait (W&W) strategy. | From date of baseline measure of ctDNA (i.e., number of mutant molecules per mL) to date of until the date of first documented progression, up to 3 years. | 
| Positive ctDNA after completing TNT | The proportion of ctDNA positive participants (at baseline, throughout TNT, and follow-up) and its exact 95% CI will be evaluated using the ctDNA analysis set. Where appropriate, sub-analyses will be conducted using populations that underwent surgery or were monitored using a W&W strategy. | From date of baseline measure of ctDNA (i.e., number of mutant molecules per mL) to date of until the date of first documented progression, up to 3 years | 
| Rate of transabdominal surgery | Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented. | Up to 3 years following completion of TNT | 
| Rate of pathological complete response (pCR) | Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented. | From start of treatment until completion of surgery, up to 3 years. | 
| Rate of watch and wait strategy | Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented. | Up to 3 years following completion of TNT | 
| Disease-free survival | Will be estimated using the Kaplan-Meier method. | Time between the date of surgery (or W&W population, the date of completing TNT) and the date of local or metastatic recurrence or death from any cause, assessed up to 3 years following completion of TNT | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | Time between the date of signed consent to the date of death from any cause, assessed up to 3 years following completion of TNT |