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

2026年8月18日 更新者：Peking University Cancer Hospital & Institute

Safety and Efficacy of Molecular-guided Non-operative Management and Organ Preservation Strategy After Precision Therapy in Gastrointestinal Cancers: A Single-center Bidirectional Cohort Study

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.

調査の概要

状態

まだ募集していません

条件

詳細な説明

The NOMAD-GI study is a single-center, bidirectional cohort study designed to evaluate the safety and clinical effectiveness of molecular biomarker-guided precision therapy followed by non-operative management (NOM) or organ-preservation strategies in patients with gastrointestinal cancers.

The central hypothesis of the study is that a subset of gastrointestinal cancers with favorable molecular characteristics may achieve a deep and durable tumor response after appropriately selected precision therapy. In carefully selected patients with a complete or near-complete clinical response, a multidisciplinary team (MDT) may identify patients in whom radical surgery can potentially be avoided while maintaining acceptable oncological safety and preserving organ function.

The study is designed to investigate a treatment paradigm in which molecular characteristics are integrated with treatment response and clinical characteristics to support individualized treatment decisions. Molecular biomarkers are therefore considered part of a multidimensional decision-making framework rather than isolated determinants of treatment allocation.

Molecular biomarkers in this study are used primarily to guide the selection of precision therapy rather than to directly determine eligibility for non-operative management. The molecular profile may include immune-related biomarkers, such as mismatch repair deficiency or microsatellite instability-high status, pathogenic POLE or POLD1 alterations, high tumor mutational burden, programmed death ligand 1 combined positive score, and Epstein-Barr virus positivity, as well as biomarkers associated with targeted treatment, such as HER2, CLDN18.2, FGFR2, MET, NTRK, KRAS G12C, and other clinically actionable molecular alterations.

The specific precision therapy received by each participant will be determined according to tumor type, disease stage, molecular characteristics, approved indications, contemporary clinical practice, and the treating multidisciplinary team. Precision therapy may include immune checkpoint inhibitors, targeted therapies, chemotherapy combined with immunotherapy or targeted therapy, or other clinically appropriate systemic treatment approaches.

After precision therapy, treatment response will be evaluated using appropriate clinical, radiological, endoscopic, and pathological assessments according to the primary tumor site. Patients with a favorable response, including clinical complete response or near-complete response, may undergo MDT evaluation for potential non-operative management or organ-preservation treatment.

The MDT decision will consider tumor response, primary tumor location, baseline disease characteristics, molecular profile, treatment history, imaging findings, endoscopic findings, pathological findings when available, patient preferences, expected functional consequences of radical surgery, and the feasibility of intensive surveillance.

Patients considered suitable for non-operative management may undergo a structured watch-and-wait or active surveillance strategy. Selected patients with residual or near-complete response may undergo local treatment, including endoscopic resection or local excision, when clinically appropriate. Patients who do not meet criteria for safe organ preservation, who have persistent or progressive disease, or who require radical treatment based on MDT assessment will undergo radical surgery according to standard clinical practice.

The study includes both a retrospective cohort and a prospective cohort. The retrospective cohort will include eligible patients treated before initiation of prospective enrollment for whom sufficient clinical, molecular, treatment, response, and follow-up data are available. The prospective cohort will include eligible participants enrolled after ethics approval and informed consent, followed according to the predefined study surveillance protocol.

The primary research objective is to evaluate the proportion of patients who achieve successful organ preservation without radical surgery after molecular biomarker-guided precision therapy and MDT-directed NOM or organ-preservation treatment. Secondary objectives include evaluation of disease-free survival, overall survival, local tumor regrowth, salvage radical surgery, permanent stoma, treatment-related morbidity, and patient-reported quality of life and organ function.

The study is observational. Treatment selection, including the choice of precision therapy, NOM, organ-preservation treatment, or radical surgery, will be based on clinical decision-making and will not be assigned randomly by the study.

The presence of an actionable molecular biomarker alone does not constitute an indication for non-operative management. Non-operative management or organ-preservation treatment will only be considered after appropriate precision therapy and comprehensive response assessment, and will require MDT evaluation confirming that the anticipated oncological risk is acceptable and that intensive surveillance is feasible.

研究の種類

観察的

入学 (推定)

200

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

サンプリング方法

非確率サンプル

調査対象母集団

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.

説明

Inclusion Criteria:

  1. Adults aged 18 years or older at the time of study enrollment.
  2. Histologically confirmed gastrointestinal malignancy, including gastric cancer, gastroesophageal junction cancer, esophageal cancer, or colorectal cancer.

  3. 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.
  4. Receipt of molecular biomarker-guided precision therapy before assessment for non-operative management or organ-preservation strategy. Precision therapy may include immune checkpoint inhibitor therapy, targeted therapy, or a combination of systemic therapies according to the participant's tumor type, molecular profile, clinical stage, and standard clinical practice.
  5. After completion or adequate exposure to precision therapy, achievement of a favorable clinical response that may support consideration of non-operative management or organ-preservation strategy, including clinical complete response (cCR), near-complete response (near-cCR), major tumor regression, or other predefined favorable response categories.
  6. Multidisciplinary team (MDT) evaluation has been performed to determine whether non-operative management, local treatment, organ-preservation strategy, or radical surgery is appropriate.
  7. Adequate clinical information is available for assessment of treatment response, including appropriate imaging, endoscopic evaluation, pathological evaluation, or other clinically indicated examinations.
  8. Ability and willingness to comply with the predefined surveillance and follow-up schedule.
  9. For the prospective cohort, written informed consent is obtained before enrollment and study-specific data collection.
  10. For the retrospective cohort, eligible clinical data are available in the institutional medical records and may be used according to institutional ethics approval and applicable regulations.

Exclusion Criteria:

  1. Uncontrolled progressive metastatic disease or clinical deterioration that precludes evaluation for the study treatment strategy.
  2. Patients who are unable to undergo appropriate clinical, radiological, endoscopic, or pathological assessment required for response evaluation or follow-up.
  3. 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.
  4. Severe comorbidities or medical conditions that make continued follow-up or additional treatment evaluation clinically inappropriate.
  5. Inability or unwillingness to comply with the predefined follow-up schedule.
  6. Withdrawal of informed consent for prospective participants.
  7. Insufficient clinical information to determine eligibility, treatment response, treatment strategy, or follow-up outcomes.
  8. 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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

コホートと介入

グループ/コホート
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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
3-Year Organ Preservation Success Rate Without Radical Surgery
時間枠：3 years after initiation of the non-operative management or organ-preservation strategy

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

二次結果の測定

結果測定
メジャーの説明
時間枠
3-Year Disease-Free Survival as Determined by Clinical, Radiological, Endoscopic, and Pathological Evidence of Disease Recurrence
時間枠：3 years after initiation of the study treatment strategy

Disease-free survival is defined as the time from initiation of the non-operative management or organ-preservation strategy, or from radical surgery for participants in the radical surgery cohort, to the first documented local regrowth, local recurrence, regional recurrence, distant metastasis, second primary gastrointestinal malignancy, or death from any cause. Participants without an event at the date of last follow-up will be censored at that date.

Measure: Time to event. Unit of Measure: Months.
3 years after initiation of the study treatment strategy
3-Year Overall Survival as Determined by All-Cause Mortality
時間枠：3 years after initiation of the study treatment strategy

Overall survival is defined as the time from initiation of the non-operative management or organ-preservation strategy, or from radical surgery for participants in the radical surgery cohort, to death from any cause. Participants who are alive at the date of last follow-up will be censored at that date.

Measure: Time to event. Events: Months.
3 years after initiation of the study treatment strategy
3-Year Local Regrowth Rate Determined by Imaging, Endoscopy, and Pathological Evaluation
時間枠：3 years after initiation of the non-operative management or organ-preservation strategy

Local regrowth is defined as the reappearance of viable tumor at or adjacent to the primary tumor site after an initial clinical complete response or near-complete response during the non-operative management or organ-preservation surveillance period. Local regrowth will be assessed by magnetic resonance imaging, computed tomography, endoscopy, biopsy, or other clinically indicated diagnostic procedures.

Measure: Percentage of participants. Unit of Measure: Percentage.
3 years after initiation of the non-operative management or organ-preservation strategy
3-Year Salvage Radical Surgery Rate After Initial Non-Operative Management
時間枠：3 years after initiation of the non-operative management or organ-preservation strategy

The proportion of participants initially managed with non-operative management or an organ-preservation strategy who subsequently undergo radical surgery because of local regrowth, persistent residual disease, disease progression, inability to achieve or maintain clinical complete response, or other predefined criteria for treatment failure.

Measure: Percentage of participants. Unit of Measure: Percentage.
3 years after initiation of the non-operative management or organ-preservation strategy
3-Year Permanent Stoma Rate
時間枠：3 years after initiation of the study treatment strategy

The proportion of participants who have a permanent intestinal stoma at 3 years after initiation of the non-operative management or organ-preservation strategy or radical surgery, as applicable.

Measure: Percentage of participants. Unit of Measure: Percentage.
3 years after initiation of the study treatment strategy
Global Health Status/Quality of Life Score as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
時間枠：Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy

Global health status and quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The Global Health Status/Quality of Life scale is transformed to a score ranging from 0 to 100. Higher scores indicate better global health status and quality of life.

Measure: Score on a 0 to 100 scale. Unit of Measure: Score.
Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy
Physical Functioning Score as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
時間枠：Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy

Physical functioning will be assessed using the Physical Functioning scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The score is transformed to a range from 0 to 100. Higher scores indicate better physical functioning.

Measure: Score on a 0 to 100 scale. Unit of Measure: Score.
Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy
Low Anterior Resection Syndrome Score as Measured by the Low Anterior Resection Syndrome (LARS) Score Questionnaire in Participants With Rectal Cancer
時間枠：Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy

Bowel dysfunction will be assessed using the Low Anterior Resection Syndrome (LARS) Score questionnaire in participants with rectal cancer. The LARS Score ranges from 0 to 42, with higher scores indicating more severe bowel dysfunction. Scores of 0 to 20 indicate no LARS, 21 to 29 indicate minor LARS, and 30 to 42 indicate major LARS.

Measure: Score on a 0 to 42 scale. Unit of Measure: Score.
Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy
Gastric Cancer-Specific Quality of Life Score as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Gastric Cancer Module (EORTC QLQ-STO22)
時間枠：Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy

Gastric cancer-specific health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Gastric Cancer Module (EORTC QLQ-STO22). Scores are linearly transformed to a 0 to 100 scale. Higher scores on symptom scales indicate greater symptom burden and worse health-related quality of life.

Measure: Score on a 0 to 42 scale. Unit of Measure: Score.
Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy
Esophageal Cancer-Specific Quality of Life Score as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Cancer Module (EORTC QLQ-OES18)
時間枠：Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy

Esophageal cancer-specific health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Cancer Module (EORTC QLQ-OES18). Scores are transformed to a 0 to 100 scale. Higher scores on symptom scales indicate greater symptom burden and worse health-related quality of life.

Measure: Score on a 0 to 100 scale. Unit of Measure: Score.
Baseline, 6 months, 12 months, 24 months, and 36 months after initiation of the study treatment strategy
5-Year Overall Survival as Determined by All-Cause Mortality
時間枠：5 years after initiation of the study treatment strategy

Overall survival is defined as the time from initiation of the study treatment strategy to death from any cause. Participants who are alive at the date of last follow-up will be censored at that date.

Measure: Time to event. Unit of Measure: Months.
5 years after initiation of the study treatment strategy

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Peking University Cancer Hospital & Institute

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

  • [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.

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年9月1日

一次修了 (推定)

2030年9月1日

研究の完了 (推定)

2031年9月1日

試験登録日

最初に提出

2026年8月9日

QC基準を満たした最初の提出物

2026年8月18日

最初の投稿 (実際)

2026年8月20日

学習記録の更新

投稿された最後の更新 (実際)

2026年8月20日

QC基準を満たした最後の更新が送信されました

2026年8月18日

最終確認日

2026年8月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • NOMAD-GI-001
  • NOMAD-GI Study (レジストリ識別子：NOMAD-GI Study)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

未定

IPD プランの説明

Data may be shared upon reasonable request after publication.

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米国FDA規制機器製品の研究

いいえ

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