Safety and Efficacy of NOM and OPFS Versus RO for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers

NCT07642323 | Not Yet Recruiting DMC

• 1 other identifier: PKUCH-NORMP trial
• Study Type: observational
• Target: 22
• Locations: 0 countries
• Sites: N/A

Brief Summary

Purpose: The purpose of this study is to evaluate the safety and efficacy of Non-Operative Management (NOM) and Organ Preservation First Strategy (OPFS) compared with Radical Operation (RO) in patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) or POLE-mutated gastrointestinal cancers. Background \& Design: With the remarkable efficacy of neoadjuvant immunotherapy in dMMR/MSI-H or POLE-mutated gastrointestinal tumors, organ preservation has become a promising alternative to highly invasive surgeries. The NOR-MP trial is a single-center, bidirectional registry study consisting of two parts: a retrospective cohort study and a prospective observational registry. Intervention Group (NOM/OPFS): Patients who achieve a clinical complete response (cCR) or near-cCR after neoadjuvant immunotherapy will undergo a "Watch \& Wait" (W\&W) strategy. Patients with near-cCR or non-cCR who are eligible for organ preservation will undergo local excision (LE) or endoscopic resection (including ESD or EMR). Comparison Group (Radical Operation): Patients who undergo standard radical surgical resection after neoadjuvant immunotherapy. The study aims to determine whether an organ-preserving approach can achieve comparable oncological outcomes and safety profiles while significantly improving patients' quality of life compared to radical surgery.

Conditions

Gastrointestinal Cancers; Gastrointestinal Cancers - Stomach; Gastrointestinal Cancers - Colorectal; Gastrointestinal Cancers - Anus

Keywords

Gastrointestinal cancers; Colorectal cancer; Gastric cancer

Outcome Measures

Primary Outcomes (1)

• Organ Preservation Rate (for OPFS/NOM group)

  The percentage of patients in the NOM/OPFS group who successfully maintain their native organ without requiring radical surgical resection or permanent stoma.

  Up to 3 years after the completion of neoadjuvant immunotherapy.

Secondary Outcomes (5)

• Surgical Safety and Postoperative Complications

  Within 30 days and 90 days post-surgery.

• Pathological Response Distribution (for RO group)

  At the time of radical surgery (typically within 4-12 weeks post-immunotherapy).

• Local Regrowth / Recurrence Rate

  Followed up at regular intervals (every 3-6 months) up to 3 years.

• Overall Survival (OS)

  Up to 5 years.

• Disease-Free Survival (DFS) / Disease-Specific Survival (DSS)

  From enrollment/treatment initiation up to 5 years.

Study Arms (2)

Experimental Cohort (NOM/OPFS)

Retrospective Cohort Study: Patients who achieved cCR/near-cCR after neoadjuvant immunotherapy and entered the "Watch \& Wait" (W\&W) program, as well as those with near-cCR or non-cCR who underwent local excision (LE) or endoscopic resection (including Endoscopic Submucosal Dissection \[ESD\] or Endoscopic Mucosal Resection \[EMR\]). Prospective Registry Study: Patients eligible for and consenting to NOM or OPFS. This includes the W\&W strategy for those achieving cCR/near-cCR, and LE or endoscopic resection (ESD/EMR) for those with near-cCR or non-cCR.

Other: NOM/OPFS

Control Cohort (RO)

Retrospective Cohort Study: Patients who underwent radical surgical operation after neoadjuvant immunotherapy. Pathological outcomes (including the proportions of ypCR, ypTisN0, and ypT1-2N0) and surgical safety data will be collected and analyzed. Prospective Registry Study: Patients who proceed to standard radical operation. Pathological response distribution (proportions of ypCR, ypTisN0, ypT1-2N0, and ypT3+ diseases) and short-to-long-term surgical safety endpoints will be prospectively documented.

Interventions

NOM/OPFS OTHER

Patients eligible for and consenting to NOM or OPFS. This includes the W\&W strategy for those achieving cCR/near-cCR, and LE or endoscopic resection (ESD/EMR) for those with near-cCR or non-cCR.

Experimental Cohort (NOM/OPFS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The target population consists of adult patients diagnosed with primary gastrointestinal cancers (including but not limited to colorectal cancer, gastric cancer, and gastroesophageal junction cancer) that are histologically confirmed as deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) or harboring polymerase epsilon (POLE) exonuclease domain mutations. All enrolled patients must have received or are scheduled to receive neoadjuvant or conversion immunotherapy prior to definitive local tumor management strategy determination.

You may qualify if:

• Histologically confirmed primary gastrointestinal adenocarcinoma or squamous cell carcinoma (e.g., colorectal cancer, gastric cancer, gastroesophageal junction cancer).
• Confirmed as deficient mismatch repair (dMMR) by immunohistochemistry (IHC), high microsatellite instability (MSI-H) by polymerase chain reaction (PCR) or next-generation sequencing (NGS), or harboring POLE exonuclease domain mutations.
• Received neoadjuvant/conversion immunotherapy (immune checkpoint inhibitors, either monotherapy or combination therapy) prior to treatment response evaluation.
• For the Retrospective Cohort (Part 1): Patients treated between \[Start Month/Year\] and \[End Month/Year\] who completed evaluation and subsequent strategy (NOM/OPFS or RO).
• For the Prospective Cohort (Part 2): Newly diagnosed patients who consent to long-term follow-up and multi-disciplinary team (MDT) assessment for organ preservation or radical surgery.
• Age ≥ 18 years at the time of diagnosis.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

You may not qualify if:

• Concurrently diagnosed with other active malignant tumors within the past 5 years.
• Patients with proficient mismatch repair (pMMR) / microsatellite stable (MSS) tumors, or wild-type POLE status.
• Evidence of untreatable distant metastasis or systemic disease that precludes local tumor management (NOM/OPFS or radical operation).
• Inability to undergo regular endoscopic, radiological (MRI/CT), or clinical follow-up due to compliance or geographic reasons.
• Refusal to sign the informed consent form (applicable to the prospective cohort).

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Colorectal Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Central Study Contacts

Xiaokang Lei, M.D.

CONTACT

+8618811181993; lxkpku@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: June 6, 2026
• First Posted: June 11, 2026
• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2030
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share