Circulating Tumor DNA to Monitor the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to use the SignateraTm assay created from rectal tumor biopsies to monitor participants' blood for fragments of DNA shed by tumor cells. The tumor DNA fragments are referred to as circulating tumor DNA, or ctDNA for short.

Detailed Description
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Rectal cancer tissue samples that were collected from participants' previous biopsies will be sent to Natera for Signatera assay creation after enrollment onto the study. One 6 mL tube of blood will be obtained at baseline prior to initiation of treatment. Blood will also be obtained in two 6 tubes at the following points: 3-4 weeks into chemoradiation therapy (CRT), after CRT, after chemotherapy, after surgery for those who undergo resection, and during surveillance 3 months after surgery or at the end of treatment for one year after completion of TNT (total neoadjuvant therapy). The primary objective of the study is to estimate the percentage of patients with positive ctDNA at the end of TNT . The secondary objectives of the study include: Estimating the change in ctDNA after chemoradiation and chemotherapy Characterize the correlation of complete response to TNT with presence or absence of ctDNA Describe the recurrence rate in participants with and without ctDNA after TNT Characterize the correlation of ctDNA at end of TNT with recurrence free survival at 2 years.

Official Title
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Circulating Tumor DNA to Monitor the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer

Conditions
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Colorectal Cancer, Rectal Cancer

Intervention / Treatment
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* Genetic: SignateraTM assay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly histologically documented rectal adenocarcinoma or biopsy-proven adenoma with MRI rectum and CT chest/abdomen or PET/CT imaging consistent with stage II or III disease Plan is for participant to undergo standard TNT with induction chemoradiation Age ≥ 18 years of age Exclusion Criteria: Stage I, recurrent, or metastatic rectal cancer Received prior therapy for this rectal cancer No baseline tumor biopsies with adenocarcinoma or adequate amount of tissue from biopsies available to send for SignateraTM assay development

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

| Intervention/Treatment |
| --- |
|Genetic: SignateraTM assay|A customized tumor-informed ctDNA test that, after receiving the tumor tissue, examines whole exome sequencing of a biopsied tumor to find the somatic tumor-derived mutations. From those mutations, the 16 most clonal mutations are used to create a personal assay|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detectable ctDNA at the Completion of TNT | The percentage of participants with detectable ctDNA at the completion of TNT | up to 24 months after TNT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ctDNA | The change in ctDNA (continuous and categorical positive/negative) during and at the end of neoadjuvant chemoradiation and with chemotherapy will be measured. Continuous measurements will be summarized using medians and ranges. Categorical factors will be summarized using frequencies and percentages. Changes in ctDNA will be analyzed by using the Mann-Whitney U test or the Fisher's exact test for continuous or categorical variables, respectively. | up to 24 months after TNT | 
| Correlation of Complete Response TNT | Correlation of complete response to TNT defined by presence or absence of ctDNA. | Up to 24 months after TNT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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total neoadjuvant treatment, tumor-specific assay, Circulating Tumor DNA, ctDNA