The Surveillance Nonoperative Watch & Wait (SNOWW) Rectal Cancer Trial. (SNOWW)

The Surveillance Nonoperative Watch & Wait (SNOWW) Rectal Cancer Trial

The primary objectives of this study are to determine if the inclusion of ctDNA testing in the evaluation and management of stages 2 and 3 rectal cancers will allow clinicians to improve their selection of patients for wait and watch (WW) management and to facilitate the detection of cancer regrowth during WW surveillance.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer of the Rectum

Detailed Description

This will be a prospective multi-center observational study for adult patients with stage 2 or 3 rectal adenocarcinoma who will be treated with TNT and are potential candidates for WW management. Study eligibility will be determined prior to the initiation of TNT by individual site investigators with the expectation that both the patient and investigator will be involved in multidisciplinary cancer decision-making. The rectal cancer tissue samples that were used to make the cancer diagnosis will also be used by our collaborative sponsor (Natera, Inc) to develop a tissue-informed and patient-specific ctDNA profile for each study patient. Patient blood samples will then be collected before the start of TNT, during TNT, after the completion of TNT, and for WW patients, at the time of every scheduled endoscopic surveillance exam, as recommended by the NCCN, and when non-scheduled endoscopic exams are performed. Figure 1. The patients will be prospectively followed for 2 years after the initiation of W&W or until cancer regrowth is suspected or confirmed and treatments other than WW are implemented. Patients who have cancer regrowth and then salvage surgery will be followed until their first postoperative cancer re-staging examination. Patients who have cancer regrowth and do not have salvage surgery will be followed. until this decision to not pursue salvage surgery is made.

The study surgeons and their patients will have access to their ctDNA test results. The study surgeon and other members of the patients' cancer care team will be advised to consider these results in their patient care decision-making and to document how each ctDNA effected decision making, if at all. The study surgeon will be responsible for ensuring that their patients are aware of the limitations of ctDNA testing and the NCCN recommendations for its use in WW management of rectal cancer.

To evaluate the impact of ctDNA on the shared decision-making process, the validated 9 Item Shared Decision-Making Questionnaire (SDM-Q-9) and the Control Preference Sale (CPS) will be administered to patients at the re-staging visit following TNT, when the decision to pursue WW or surgery is being considered. For patients managed with WW, the SDM-Q-9 will also be re-administered every time ctDNA is used in surveillance and whether a treatment decision is being actively reconsidered based on ctDNA results.

Additionally, the Shared Decision-Making Questionnaire- Physician Version (SDM-Q-Doc) will be completed by study surgeons at the re-staging visit following TNT, when the decision to pursue WW or surgery is being considered. For patients managed with WW, the SDM-Q-Doc will also be re-administered every time ctDNA is used in surveillance and whether a treatment decision is being actively reconsidered based on ctDNA results. This will allow assessment of surgeon perspectives on the decision-making process and how ctDNA influences clinical recommendations

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Tracey Mac, BA BS CCRC; Phone Number: 3037242757; Email: tracey.macdermott@cuanschutz.edu
• Study Contact Backup: Name: Nargis Kalia, MPH; Phone Number: 303-724-0333; Email: nargis.kalia@cuanshcutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Rectal Cancer Stage II or III

Description

Inclusion Criteria:

1. Provision to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the duration of the study.

Additional Inclusion Criteria:

Pre-TNT phase Adult male and female patients (>18 years old) Clinical stage 2 or 3 rectal cancer, within or beyond the reach of digital rectal exam (DRE), who are evaluated in a multidisciplinary setting and who will receive induction or consolidation total neoadjuvant therapy (TNT) and are candidates for watch and wait management (WW) with curative intent.

Post-TNT phase complete or near complete clinical response to TNT High-definition flexible endoscopy: Pale smooth scar with or without telangiectasia No ulceration, nodularity, or mucosal irregularities No stricture DRE: Smooth, flat scar No nodularity Diffusion-weighted MRI2 Fibrotic, linear scar with low signal intensity on T2-weighted images No diffusion restriction No suspicious lymph nodes

Near Complete Clinical Response:

Endoscopic appearance with irregular small mucosal nodules, superficial ulceration, or mild persistent erythema DRE: Smooth induration or superficial minor mucosal irregularity MRI: T2-weighted MRI with downstaging with or without residual fibrosis, small area of residual signal, and complete or partial regression of lymph nodes. Diffusion-weighted MRI with small area of residual high signal intensity

Exclusion Criteria:

• • Patients who are less than 18 years old

  • Patients who are pregnant during the study period
  • Patients with stage I or IV rectal cancer
  • Patients who receive neoadjuvant therapy other than TNT.
  • Patients who receive short-course neoadjuvant radiotherapy.
  • Patients who are actively enrolled in other clinical trials that prohibit inclusion in this study.
  • Patients who refuse or are unable to undergo ctDNA testing and subsequent follow ups
  • Patients who refuse or are unable to undergo WW management of rectal cancer.
  • Patients who are undergoing "WW" management of rectal cancer due to refusal of recommended surgical resection. (For example, the hypothetical patient with an incomplete clinical response to TNT who refuses surgery).
  • Patients who undergo WW for palliation only.
  • Patients with prior history of rectal cancer with or without chemoradiation treatment or surgical resection
  • Patients who have a different cancer, in addition to rectal cancer, in whom the study ctDNA testing would be uninterpretable.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Rectal Cancer Clinical Stage II or III

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improve selection of patients for WW management	determine if the inclusion of ctDNA testing in the evaluation and management of stages 2 and 3 rectal cancers will allow clinicians to improve their selection of patients for WW management and to facilitate the detection of cancer regrowth during WW surveillance.	36 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Natera, Inc.
• Investigators: Principal Investigator: Jon MT Vogel, MD, University of Colorado Denver Anschutz Medical Campus

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 5, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Management of Stage 2 or 3 Rectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: 25-1647.cc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: A plan has not been put in place at this time

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No