Non-Operative Management and Following Immunotherapy for Colorectal Cancer and Other GI Cancers (NOMIC)

Non-Operative Management and Following Immunotherapy for Colorectal Cancer and Other GI Cancers (NOMIC Trial)

This is a single-center, bidirectional (retrospective and prospective) registry study aimed at evaluating the safety and efficacy of Non-Operative Management (NOM) and Organ-Preserving Functional Surgery (OPFS) in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) or POLE-mutated gastrointestinal (GI) cancers who received neoadjuvant immunotherapy.Patients achieving a clinical complete response (cCR) or near-cCR may undergo a "Watch & Wait" (W&W) strategy, while those with near-cCR or non-cCR ($\le ymrT2N0$) may undergo local excision (LE) or endoscopic resection (ESD/EMR). Patients undergoing radical operation (RO) will serve as the control cohort to compare oncological outcomes and safety data.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastrointestinal Cancer; Colorectal (Colon or Rectal) Cancer; Stomach (Gastric) Cancer
• Intervention / Treatment: Other: NOM; Other: RO

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Lin Wang Prof., M.D.; Phone Number: 13910975011; Email: wanglinmd@foxmail.com
• Study Contact Backup: Name: Xiaokang Lei Dr., M.D.

Study Locations

• China
  • Haidian District
    • Beijing, Haidian District, China, 100142
      • Peking University Cancer Hospital
      • Contact: Xiaokang Lei Dr., M.D.; Phone Number: 18811181993; Email: lxkpku@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) or POLE-mutated gastrointestinal (GI) cancers who received neoadjuvant immunotherapy.

Description

Inclusion Criteria:

1. Retrospective Cohort Inclusion Criteria

   • Pathologically confirmed gastrointestinal malignancy determined as MSI-H/dMMR or POLE mutation, and initially resectable.
   • Completed prior immunotherapy.
   • No evidence of distant metastasis.
   • Managed with W&W, LE, endoscopic surgery, or radical operation after treatment.

2. Prospective Cohort Inclusion Criteria

   • Pathologically confirmed gastrointestinal malignancy determined as MSI-H/dMMR or POLE mutation, and initially resectable.
   • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
   • Immunotherapy status: naive, currently receiving, or completed treatment, and evaluated by the PKUCH-NOMIC research group as cCR/near-cCR or Non-cCR (≤ ymrT2N0).
   • No evidence of distant metastasis.
   • Absence of emergencies requiring immediate surgery (e.g., hemorrhage, perforation, obstruction).

Exclusion Criteria:

• Recurrent gastrointestinal tumors.Initial presence of unresectable distant metastases.
• Serum creatinine > 1.5 times upper limit of normal (ULN).
• History of pelvic radiation therapy.Inability to tolerate MRI examinations.
• History of other malignancies within the past 5 years with a survival rate significantly lower than the historical rectal cancer survival data of this center (except adequately treated basal cell carcinoma, cutaneous squamous cell carcinoma, small renal cell carcinoma, breast cancer, and papillary thyroid carcinoma).
• Arterial thromboembolic events within the past 6 months (e.g., angina, myocardial infarction, transient ischemic attack [TIA], cerebral vascular accident [CVA]).
• Prior receipt of other types of investigational anti-tumor therapies.
• Pregnant or lactating women.
• Concomitant diseases or mental health conditions that may interfere with study participation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental Cohort (NOM); Patients achieving a clinical complete response (cCR) or near-cCR may undergo a "Watch & Wait" (W&W) strategy, while those with near-cCR or non-cCR (≤ymrT2N0$) may undergo local excision (LE) or endoscopic resection (ESD/EMR).	Other: NOM; Patients achieving a clinical complete response (cCR) or near-cCR may undergo a "Watch & Wait" (W&W) strategy, while those with near-cCR or non-cCR (≤ymrT2N0) may undergo local excision (LE) or endoscopic resection (ESD/EMR).
Control arm; Patients undergoing radical operation (RO) will serve as the control cohort to compare oncological outcomes and safety data.	Other: RO; Patients undergoing radical operation (RO) will serve as the control cohort to compare oncological outcomes and safety data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ Preservation Rate	The proportion of patients successfully managed with NOM without the need for supplementary radical surgery, loss of organ function, or a permanent stoma (specifically for rectal cancer patients).	3 years after the completion of neoadjuvant immunotherapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the start of treatment to death from any cause.	Up to 5 years.
Surgical Safety and Postoperative Complications	Incidence and severity of perioperative complications classified by the Clavien-Dindo grading system, comparing RO, LE, and endoscopic resection (ESD/EMR).	3 years after the completion of neoadjuvant immunotherapy.
Distribution of Pathological Response (RO Group Only)	Percentage of patients achieving ypCR, ypTisN0, ypT1-2N0, and ypT3+ in the radical surgery cohort to characterize pathological response after immunotherapy.	At the time of radical surgery (typically 4-12 weeks post-immunotherapy).
Local Regrowth Rate	The proportion of patients experiencing local tumor regrowth in the W&W group or after local/endoscopic excision.	Regular follow-up every 3-6 months for up to 3 years.
Disease-Free Survival (DFS)	Time from the initiation of neoadjuvant immunotherapy to the first documentation of disease recurrence (local, regional, or distant), progression, or death from any cause, comparing the NOM/OPFS group with the RO group.	Up to 5 years from enrollment/treatment initiation.

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 15, 2029
• Study Completion (Estimated): October 15, 2030

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: dMMR/MSI-H; POLE-mutated
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Stomach Neoplasms; Colonic Neoplasms; Gastrointestinal Neoplasms
• Other Study ID Numbers: NOMIC Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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