Clinical trial · Observational
Safety and Efficacy of NOM and OPFS Versus RO for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers
Safety and Efficacy of Nonoperative Management (NOM) and Organ Preservation First Strategy (OPFS) Versus Radical Operation (RO) for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers: A Single-Center, Bidirectional Registry Study
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Gastrointestinal Cancers | Malignant Digestive System Neoplasm | ALIAS | 0.90 |
| Gastrointestinal Cancers - Anus | — | UNRESOLVED | — |
| Gastrointestinal Cancers - Colorectal | — | UNRESOLVED | — |
| Gastrointestinal Cancers - Stomach | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| NOM/OPFS | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- label
- Experimental Cohort (NOM/OPFS)
- description
- 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.
- interventionNames
- Other: NOM/OPFS
- label
- Control Cohort (RO)
- description
- 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.
Primary outcomes (1)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * 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. Exclusion Criteria: * 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).
References
Publications (0)
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