ctDNA-Informed Management of Early-Stage Rectal Cancer

Not Applicable

Not yet recruiting

• Conditions: Rectal Adenocarcinoma; Rectal Cancer; Early-stage Rectal Cancer; Locally Advanced Rectal Adenocarcinoma
• Interventions: Drug: Signatera Genome ultra-sensitive ctDNA blood test + total neoadjuvant therapy (TNT)

• Registration Number: NCT07209215
• Lead Sponsor: University of California, Davis

Brief Summary

This is a phase 2 pragmatic study to examine the utility of ctDNA-informed treatment management for participants with early-stage rectal cancer using the Signatera Genome assay. The primary aims are to 1) assess pathologic complete response (path CR) in the ctDNA informed management arm; 2) assess pathologic complete response (path CR) in the post total neoadjuvant therapy (TNT) standard of care (SOC) surgery arm; and 3) assess disease free survival (DFS) in the ctDNA informed management arm.

Detailed Description

Two cohorts of participants will be enrolled: Cohort A (participants appropriate for receiving TNT) and Cohort B (TNT already performed at UC Davis Health or externally). At Time A after TNT is completed and based on ctDNA assay results, the clinical decision will be made to put participants into one of two arms: the ctDNA informed management arm (Watchful Waiting \[WW\] surveillance) or the post TNT SOC surgery arm; participants will be monitored for ctDNA positivity for up to 5 years.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-30
• Study First Submitted QC: 2025-09-30
• Last Update Submitted: 2025-09-30
• Study First Posted: 2025-10-06
• Last Update Posted: 2025-10-06
• Study Start: 2025-11-01
• Primary Completion: 2027-11
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Tumor tissue histologically confirming rectal adenocarcinoma that is available for Natera ctDNA assay.
• Cohort A only: Patients appropriate for receiving TNT including chemotherapy and chemoradiation.
• Cohort B only: TNT must have included at least 4 cycles of CAPEOX or 6 cycles of FOLFOX and at least 45 Gy in 25 fractions to the pelvis during chemoradiation.
• Patients ≥18 years of age at time of consent.
• Ability to understand and willingness to sign the informed consent form (ICF).
• Ability and stated willingness to adhere to the study visit schedule and protocol procedures/requirements.

Exclusion Criteria

• Prior treatment for rectal cancer, except for cohort B.
• Evidence of distant metastatic disease on staging imaging (CT chest with abdominopelvic imaging by CT or MRI) within 8 weeks of enrollment.
• Patients on hemodialysis.
• Any condition that in the opinion of the investigator would interfere with the participant's safety or compliance while on trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ctDNA informed management arm (Watch and Wait surveillance)	Signatera Genome ultra-sensitive ctDNA blood test + total neoadjuvant therapy (TNT)	-
Post TNT SOC surgery arm	Signatera Genome ultra-sensitive ctDNA blood test + total neoadjuvant therapy (TNT)	-

Primary Outcome Measures

Name	Time	Method
Pathologic complete response (pathCR) rate (ctDNA Informed Management Arm)	Up to 2 years after TNT	Percent of participants with local regrowth within 2 years of total neoadjuvant therapy (TNT)
Pathologic complete response (pathCR) rate (Post TNT SOC Surgery Arm)	Up to 2 years after TNT	Percent of participants with local regrowth within 2 years of TNT
Disease-free survival (DFS) rate (ctDNA Informed Management Arm)	Up to 2 years after TNT	Median interval from first date of TNT to the first occurrence of locoregional failure, distant recurrence, a new invasive colorectal primary cancer.

Secondary Outcome Measures

Name	Time	Method
Frequency of local regrowth (ctDNA Informed Management Arm)	Up to 2 years after TNT	Percentage of participants with local regrowth within 2 years of TNT

Trial Locations

Locations (1)

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States