Clinical trial NCT05081024: Establishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal Cancer
Official title: Establishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: Natera, Inc.
First posted: 2021-10-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete clinical response (cCR)
timeFrame: From time of treatment start up to date of completing total neoadjuvant therapy (TNT), up to 3 months.
Secondary outcomes:
measure: Positive circulating tumor deoxyribonucleic acid (ctDNA)
timeFrame: 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.
measure: Positive ctDNA after completing TNT
timeFrame: 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
measure: Rate of transabdominal surgery
timeFrame: Up to 3 years following completion of TNT
measure: Rate of pathological complete response (pCR)
timeFrame: From start of treatment until completion of surgery, up to 3 years.
measure: Rate of watch and wait strategy
timeFrame: Up to 3 years following completion of TNT
measure: Disease-free survival
timeFrame: 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
measure: Overall survival
timeFrame: 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 outcomes:
measure: ctDNA status
timeFrame: 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
measure: Positive ctDNA by clinical characteristics
timeFrame: 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
measure: Sensitivity
timeFrame: 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
measure: Specificity
timeFrame: 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
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Adel Kardosh, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: