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

March 25, 2024 updated by: Adel Kardosh M.D., Ph.D., OHSU Knight Cancer Institute
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • OHSU Knight Cancer Institute
        • Contact:
        • Principal Investigator:
          • Adel Kardosh, M.D.,Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with stage II-III rectal adenocarcinoma at Oregon Health & Science University (OHSU), its affiliated community oncology (CHO) site, or collaborating research site

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Observational (biospecimen collection, medical 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.
Procedure: Biopsy
Undergo biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Other: Electronic Health Record Review
Medical records are reviewed
Procedure: Biospecimen Collection
Undergo collection of blood and/or tissue samples
Other Names:
  • Biological Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete clinical response (cCR)
Time Frame: 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.
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)
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
Up to 3 years following completion of TNT
Rate of pathological complete response (pCR)
Time Frame: 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.
From start of treatment until completion of surgery, up to 3 years.
Rate of watch and wait strategy
Time Frame: 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.
Up to 3 years following completion of TNT
Disease-free survival
Time Frame: 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.
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
Time Frame: 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.
Time between the date of signed consent to the date of death from any cause, assessed up to 3 years following completion of TNT

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
ctDNA status
Time Frame: 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 versus negative results per test results
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 by clinical characteristics
Time Frame: From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT
association or recurrence on ctDNA test and standard imaging
From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT
Sensitivity
Time Frame: From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT
Sensitivity and specificity will be calculated using complete clinical response (yes versus [vs.] no), or tumor recurrence (yes vs. no) as reference standard.
From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT
Specificity
Time Frame: From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT
Sensitivity and specificity will be calculated using complete clinical response (yes vs. no), or tumor recurrence (yes vs. no) as reference standard.
From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OHSU Knight Cancer Institute

Collaborators

Natera, Inc.

Investigators

  • Principal Investigator: Adel Kardosh, M.D.,Ph.D., OHSU Knight Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2021

Primary Completion (Estimated)

September 3, 2024

Study Completion (Estimated)

September 3, 2024

Study Registration Dates

First Submitted

September 7, 2021

First Submitted That Met QC Criteria

October 4, 2021

First Posted (Actual)

October 18, 2021

Study Record Updates

Last Update Posted (Actual)

March 26, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00022247 (Other Identifier: OHSU Knight Cancer Institute)
  • NCI-2021-08733 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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