NOMAD-GI: Molecular-guided Non-operative Management and Organ Preservation Strategy After Precision Therapy in Gastrointestinal Cancers

NCT07775859 | Not Yet Recruiting

• 2 other identifiers: NOMAD-GI-001NOMAD-GI Study
• Study Type: observational
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

The NOMAD-GI study is a single-center, bidirectional cohort study designed to evaluate the safety and efficacy of molecular biomarker-guided non-operative management (NOM) and organ preservation strategies after precision therapy in patients with gastrointestinal cancers. Patients with actionable molecular biomarkers, including dMMR/MSI-H, POLE mutation, PD-L1 high expression, tumor mutational burden-high (TMB-H), Epstein-Barr virus positivity (EBV+), HER2 positivity, CLDN18.2 positivity, and other actionable genomic alterations, will be enrolled. After immune checkpoint inhibitor or targeted therapy, patients achieving favorable clinical responses will undergo multidisciplinary team (MDT) evaluation and receive either non-operative management, local treatment, or radical surgery according to individualized treatment decisions. The study aims to establish a molecular-driven organ preservation paradigm for gastrointestinal cancers and evaluate whether NOM can provide comparable oncological outcomes while improving functional outcomes and quality of life.

Conditions

Gastrointestinal Cancer; Gastric Cancer; Gastroesophageal Junction Cancer; Esophageal Cancer; Colorectal Cancer

Keywords

Precision oncology; Molecular biomarkers; Gastrointestinal cancer; Non-operative management; Organ preservation; Immunotherapy; Targeted therapy; Watch and wait; Multidisciplinary treatment

Outcome Measures

Primary Outcomes (1)

• 3-Year Organ Preservation Success Rate Without Radical Surgery

  The proportion of participants who remain free from radical surgical resection and maintain the originally targeted organ at 3 years after initiation of the non-operative management or organ-preservation strategy. Organ preservation success will be assessed using clinical records, imaging, endoscopic evaluation, pathological evaluation when applicable, and subsequent treatment records. Measure: Percentage of participants Unit of Measure: Percentage

  3 years after initiation of the non-operative management or organ-preservation strategy

Secondary Outcomes (11)

• 3-Year Disease-Free Survival as Determined by Clinical, Radiological, Endoscopic, and Pathological Evidence of Disease Recurrence

  3 years after initiation of the study treatment strategy

• 3-Year Overall Survival as Determined by All-Cause Mortality

  3 years after initiation of the study treatment strategy

• 3-Year Local Regrowth Rate Determined by Imaging, Endoscopy, and Pathological Evaluation

  3 years after initiation of the non-operative management or organ-preservation strategy

• 3-Year Salvage Radical Surgery Rate After Initial Non-Operative Management

  3 years after initiation of the non-operative management or organ-preservation strategy

• 3-Year Permanent Stoma Rate

  3 years after initiation of the study treatment strategy

Study Arms (2)

Molecular-guided NOM/Organ Preservation Cohort

Patients receiving molecular-guided precision therapy followed by multidisciplinary evaluation and managed with: * Watch-and-wait strategy; * Endoscopic resection; * Local excision; * Other organ-preserving approaches.

Radical Surgery Cohort

Patients receiving radical surgical resection after precision therapy. Procedures include: * Radical gastrectomy; * Radical colorectal resection; * Esophagectomy. Participants will not be assigned to a treatment group by the study. The cohort classification will be based on the treatment strategy actually received after precision therapy and MDT evaluation.

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 study population will consist of adult patients with histologically confirmed gastrointestinal cancers who are treated at Peking University Cancer Hospital and who have at least one actionable molecular biomarker relevant to immune checkpoint inhibitor therapy, targeted therapy, or other precision treatment strategies. Eligible participants will be identified from the institutional gastrointestinal oncology clinical practice and research database and enrolled into retrospective or prospective cohorts according to the availability of eligible clinical data and the timing of study enrollment.

You may qualify if:

• Adults aged 18 years or older at the time of study enrollment.
• Histologically confirmed gastrointestinal malignancy, including gastric cancer, gastroesophageal junction cancer, esophageal cancer, or colorectal cancer.
• Presence of at least one molecular biomarker that may support selection of precision therapy, including but not limited to:
• Mismatch repair deficiency or microsatellite instability-high (dMMR/MSI-H);
• Pathogenic or likely pathogenic POLE or POLD1 mutation;
• High programmed death ligand 1 combined positive score (PD-L1 CPS), when applicable to the tumor type and treatment strategy;
• Tumor mutational burden-high (TMB-H);
• Epstein-Barr virus-positive status (EBV-positive), when applicable;
• Human epidermal growth factor receptor 2 (HER2) positivity;
• Claudin 18.2 (CLDN18.2) positivity;
• Fibroblast growth factor receptor 2 (FGFR2) alteration;
• Mesenchymal-epithelial transition factor (MET) amplification or other actionable MET alteration;
• Neurotrophic tyrosine receptor kinase (NTRK) gene fusion;
• Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation;
• Other clinically actionable molecular alterations recognized according to contemporary clinical practice.

You may not qualify if:

• Uncontrolled progressive metastatic disease or clinical deterioration that precludes evaluation for the study treatment strategy.
• Patients who are unable to undergo appropriate clinical, radiological, endoscopic, or pathological assessment required for response evaluation or follow-up.
• Previous treatment history or concurrent medical conditions that, in the judgment of the multidisciplinary team, preclude reliable assessment of tumor response or implementation of the predefined surveillance strategy.
• Severe comorbidities or medical conditions that make continued follow-up or additional treatment evaluation clinically inappropriate.
• Inability or unwillingness to comply with the predefined follow-up schedule.
• Withdrawal of informed consent for prospective participants.
• Insufficient clinical information to determine eligibility, treatment response, treatment strategy, or follow-up outcomes.
• Patients with conditions that require immediate radical surgery or other urgent treatment according to multidisciplinary clinical assessment and who cannot safely undergo the predefined study evaluation.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Related Publications (1)

• [1] SUNG H, FILHO A M, LAVERSANNE M, et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries [J]. CA Cancer J Clin, 2026, 76(4): e70090. [2] SUN K X, LI L, WANG S M, et al. [Cancer incidence and mortality across diverse geographical regions in China, 2024] [J]. Zhonghua Zhong Liu Za Zhi, 2026, 48(3): 400-12. [3] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer (Version 2.2026). Published March 2026. Accessed August 8, 2026. https://www.nccn.org/guidelines/guidelines-detail?id=1428 [J]. [4] FOKAS E, APPELT A, GLYNNE-JONES R, et al. International consensus recommendations on key outcome measures for organ preservation after (chemo)radiotherapy in patients with rectal cancer [J]. Nature Reviews Clinical Oncology, 2021, 18(12): 805-16. [5] HABR-GAMA A, PEREZ R O, NADALIN W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results [J]. Ann Surg, 2004, 240(4): 711-7; discussion 7-8. [6] MUZNY D M, BAINBRIDGE M N, CHANG K, et al. Comprehensive molecular characterization of human colon and rectal cancer [J]. Nature, 2012, 487(7407): 330-7. [7] SADANANDAM A, LYSSIOTIS C A, HOMICSKO K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy [J]. Nat Med, 2013, 19(5): 619-25. [8] BASS A J, THORSSON V, SHMULEVICH I, et al. Comprehensive molecular characterization of gastric adenocarcinoma [J]. Nature, 2014, 513(7517): 202-9. [9] LE D T, URAM J N, WANG H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency [J]. N Engl J Med, 2015, 372(26): 2509-20. [10] LE D T, DURHAM J N, SMITH K N, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade [J]. Science, 2017, 357(6349): 409-13.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Collected biomarkers include: Immune-related biomarkers: 1. MSI/MMR status; 2. POLE/POLD1 mutation; 3. PD-L1 CPS; 4. TMB; 5. EBV. Target-related biomarkers: 1. HER2; 2. CLDN18.2; 3. FGFR2; 4. MET; 5. NTRK; 6. KRAS G12C.

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

lei, M.D.

CONTACT

+8601088196086; lxkpku@gmail.com

Yingjie Li, M.D.

CONTACT

+8613520186618; liyingjiedr@sina.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2026
• First Posted: August 20, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031
• Last Updated: August 20, 2026

Record last verified: 2026-08