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

Rectal Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05081024
• Other study ID #: STUDY00022247
• Secondary ID: NCI-2021-08733ST
• Status: Recruiting
• Start date: September 3, 2021
• Est. completion date: September 3, 2024

Study information

• Verified date: March 2024
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 3, 2024
• Est. primary completion date: September 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Rectal Adenocarcinoma
• Rectal Neoplasms
• 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

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo collection of blood and/or tissue samples

Other:
• Electronic Health Record Review
Medical records are reviewed

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	Natera, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ctDNA status	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
Other	Positive ctDNA by clinical characteristics	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
Other	Sensitivity	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
Other	Specificity	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
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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