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

Recruiting

• Conditions: Stage II Rectal Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8; Rectal Adenocarcinoma; Stage IIA Rectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IIB Rectal Cancer AJCC v8; Stage IIC Rectal Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8
• Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Other: Electronic Health Record Review

• Registration Number: NCT05081024
• Lead Sponsor: OHSU Knight Cancer Institute

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-09-03
• Study First Submitted: 2021-09-07
• Study First Submitted QC: 2021-10-04
• Study First Posted: 2021-10-18
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-24
• Primary Completion: 2025-09-03
• Study Completion: 2025-09-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (biospecimen collection, medical record review)	Biopsy	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.
Observational (biospecimen collection, medical record review)	Electronic Health Record Review	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.
Observational (biospecimen collection, medical record review)	Biospecimen Collection	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.

Primary Outcome Measures

Name	Time	Method
Complete clinical response (cCR)	From time of treatment start up to date of completing total neoadjuvant therapy (TNT), up to 3 months.	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.

Secondary Outcome Measures

Name	Time	Method
Rate of transabdominal surgery	Up to 3 years following completion of TNT	Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented.
Rate of watch and wait strategy	Up to 3 years following completion of TNT	Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented.
Overall survival	Time between the date of signed consent to the date of death from any cause, assessed up to 3 years following completion of TNT	Will be estimated using the Kaplan-Meier method.
Positive circulating tumor deoxyribonucleic acid (ctDNA)	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.	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.
Rate of pathological complete response (pCR)	From start of treatment until completion of surgery, up to 3 years.	Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented.
Disease-free survival	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	Will be estimated using the Kaplan-Meier method.
Positive ctDNA after completing TNT	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	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.

Trial Locations

Locations (1)

OHSU Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States