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Radiothérapie intestinale à faible dose plus immunochimiothérapie pour la conversion du carcinome épidermoïde de l'œsophage à la limite de la résécabilité/non résécable (ILDR-03)

30 septembre 2026 mis à jour par: Chuangzhen Chen

Efficacité et sécurité de la combinaison d'une radiothérapie intestinale à faible dose plus le tislelizumab et la chimiothérapie pour la conversion du carcinome épidermoïde de l'œsophage à la limite de la résécabilité/non résécable

Esophageal cancer (EC) ranks among the leading malignant gastrointestinal tumors globally in terms of both incidence and mortality. Cases of EC in China account for over 50% of the global total, with squamous cell carcinoma being the primary pathological type. Locally advanced EC (LAEC), particularly cases where radical surgical resection is not feasible, exhibits high recurrence rates and low 5-year survival rates. However, studies have shown that patients with LAEC who undergo comprehensive treatment followed by surgery experience significantly prolonged survival and improved quality of life compared to those who do not receive surgical intervention.

Current conversion treatment regimens under investigation include: chemotherapy alone, chemoradiotherapy, immunotherapy combined with chemotherapy, and immunotherapy combined with chemoradiotherapy-each of these approaches has distinct advantages and limitations. Immunochemotherapy has emerged as a current research focus: it not only demonstrates significantly superior efficacy compared to chemotherapy alone but also exhibits lower cumulative toxicity than radiotherapy-combined conversion regimens, resulting in a more favorable overall benefit-risk ratio. As such, it represents the most promising conversion treatment strategy.

Retrospective and prospective clinical studies have shown that low-dose radiotherapy targeting the small intestine can enhance the anti-tumor response of immune checkpoint inhibitors (ICIs) in patients with advanced solid tumor, prolong their overall survival, and increase the incidence of the abscopal effect. Further mechanistic investigations have revealed that intestinal low-dose radiotherapy (ILDR) may augment the immune cancerous lethality by modulating the gut microbiota and their metabolic profiles.

Based on the findings from these preliminary studies, the current research plans to conduct a prospective phase II single-arm clinical trial to investigate the efficacy and safety of ILDR combined with immunochemotherapy as conversion therapy in patients with borderline resectable or unresectable esophageal squamous cell carcinoma (BR/UR ESCC). This research plans to enroll at least 39 evaluable cases or a total of 39 cases in two seperated stages, focusing on patients with thoracic BR/UR ESCC. Patients will receive a single fraction of ILDR with a mean dose of 1 Gy, concurrently with 3 cycles of albumin-bound paclitaxel (260 mg/m² on day 1), cisplatin (75 mg/m² on day 1), and tislelizumab (200 mg on day 1). The efficacy and safety of the treatment will be evaluated throughout the study.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

39

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Chine
    • Guangdong
      • Shantou, Guangdong, Chine, 515031
        • Recrutement
        • Cancer Hospital, Shantou University Medical College
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Patients voluntarily enroll in this study, sign an informed consent form, and demonstrate good compliance.

  2. Age ≥18 years and ≤75 years; both sexes are eligible.

  3. ECOG performance status score of 0-1.

  4. Pathologically confirmed esophageal squamous cell carcinoma (ESCC) prior to surgery.

  5. Thoracic esophageal cancer.

  6. Unresectable lesions, defined as: T4 stage; Borderline resectable T3 disease, in which imaging cannot exclude invasion of adjacent organs or structures, such as the trachea, bronchi, or aorta; T3 disease with supraclavicular lymph node metastasis; or clinically confirmed unresectable disease by the surgeon.

  7. No prior history of anti-tumor treatment, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy.

  8. Baseline laboratory requirements (within 7 days prior to enrollment):

    Hematology:

    1. Hb≥90 g/L (no transfusion within 14 days)
    2. NEUT ≥1.5×10⁹/L
    3. PLT ≥100×10⁹/L
    4. WBC≥3×10⁹/L

    Biochemistry:

    1. ALT and AST≤2.5×ULN
    2. TBIL≤1.5×ULN
    3. SCr≤1.5×ULN; or CrCl≥60 mL/min Coagulation: APTT, INR, and PT≤1.5×ULN Thyroid function: TSH≤ULN (if abnormal, FT3/FT4 levels should also be considered; eligible if FT3/FT4 are normal) Echocardiography: LVEF≥50%

  9. Female subjects need to agree to use contraception during the study and for 6 months post-study; serum pregnancy test negative within 7 days prior to enrollment; non-lactating. Male subjects must agree to use contraception during the study and for 6 months post-study.

  10. No psychological, familial, social, or geographical factors that may impair protocol adherence.

  11. Other parameters meet general clinical trial enrollment criteria.

  12. The subject or authorized representative has read, fully understands the patient information sheet, and signed the informed consent form.

Exclusion Criteria:

  1. Patients with distant metastases other than supraclavicular lymph node metastases.
  2. Presence or high risk of esophageal perforation.
  3. Patients with contraindications to radiotherapy or immune checkpoint inhibitor (ICI) therapy.
  4. Subjects with active, uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment.
  5. Respiratory depression, airway obstruction, or tissue hypoxia.
  6. Severe cardiac disease (i.e., NYHA functional class II or higher).
  7. Markedly abnormal liver or kidney function (i.e., indicators >3 times the upper limit of normal).
  8. Active hepatitis B, hepatitis C, HIV, or syphilis.
  9. Active brain disease or central nervous system/meningeal metastases with significant symptoms, or impaired decision-making capacity.
  10. Hypersensitivity to drugs included in the trial.
  11. Drug and/or alcohol abuse.
  12. Pregnant or lactating women.
  13. Concurrent participation in another therapeutic clinical trial.
  14. Major surgical procedure within 30 days prior to enrollment.
  15. Use of antibiotics, antifungals, antivirals, or antiparasitics within 4 weeks prior to registration.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: ILDR plus immunochemotherapy plus surgery

1Gy/1F ILDR + albumin-bound paclitaxel (3 cycles of 260 mg/m² on day 1), cisplatin (3 cycles of 75 mg/m² on day 1), and tislelizumab (3 cycles of 200 mg on day 1) + surgery
Radiation: Intestinal Low Dose Radiotherapy-1Gy

1Gy ILDR will be administered to patients in a single fraction. The radiation treatment volume composes both the jejunum and ileum.

Médicament: PD-1/PD-L1 inhibitors

3 cycles of tislelizumab（200 mg D1 q3w）

Médicament: Chemotherapy

3 cycles of albumin-bound paclitaxel（260 mg/m2 D1 q3w）+ cisplatin（75 mg/m2 D1 q3w）

Procédure: Surgery

McKeown esophagectomy or laparoscopic-assisted McKeown esophagectomy is recommended, with either two-and-a-half-field lymphadenectomy or three-field lymph node dissection.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
1-Year Progression-Free Survival Rate (1y-PFSR)
Délai: Up to 12 months after the initiation of treatment.

The 1y-PFSR is defined as the proportion of patients who remain alive without documented cancer progression 1 year after the initiation of treatment.
Up to 12 months after the initiation of treatment.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Pathological Complete Response (pCR) Rate
Délai: From postoperative day 0 up to 15 weeks postoperatively.

The proportion of patients who, following conversion therapy, exhibit no residual invasive cancer cells in either the primary tumor site or regional lymph nodes upon pathological evaluation of surgical resection specimens, expressed as a percentage of the total treated population.
From postoperative day 0 up to 15 weeks postoperatively.
Objective Response Rate (ORR)
Délai: Baseline, every 6 weeks during conversion therapy, postoperation, every 4 months following the first postoperative assessment with a maximum duration of 12 months.

Proportion of patients achieving complete response (CR) or partial response (PR) (sustained ≥4 weeks) per RECIST v1.1 and iRECIST criteria.
Baseline, every 6 weeks during conversion therapy, postoperation, every 4 months following the first postoperative assessment with a maximum duration of 12 months.
Major Pathological Response (MPR) Rate
Délai: From postoperative day 0 up to 15 weeks postoperatively.

MPR is defined as the proportion of patients with ≤10% residual viable tumor cells in surgical specimens following treatment. Pathological evaluation requires standardized sampling and separate assessment of lymph node metastases.
From postoperative day 0 up to 15 weeks postoperatively.
Disease Control Rate (DCR)
Délai: Baseline, every 6 weeks during conversion therapy, postoperation, every 4 months following the first postoperative assessment with a maximum duration of 12 months.

DCR is defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) post-treatment, as measured by RECIST 1.1 and iRECIST criteria.
Baseline, every 6 weeks during conversion therapy, postoperation, every 4 months following the first postoperative assessment with a maximum duration of 12 months.
Adverse Event Incidence Rate
Délai: Up to 12 months after surgery.

The proportion of patients experiencing adverse events of any grade (graded according to CTCAE 6.0, Common Terminology Criteria for Adverse Events, grades 1-5) during treatment.
Up to 12 months after surgery.
1-Year Overall Survival Rate (1y-OSR)
Délai: Up to 12 months after the initiation of treatment.

The 1y-OSR is defined as the proportion of patients who have not experienced all-cause death at 12 months following the initiation of treatment.
Up to 12 months after the initiation of treatment.
Surgical Conversion Rate
Délai: Up to 12 months after surgery.

Defined as the proportion of initially unresectable patients who are converted to resectable status following treatment.
Up to 12 months after surgery.
R0 Resection Rate
Délai: From postoperative day 0 up to 15 weeks postoperatively.

Defined as the proportion of radical surgeries achieving microscopically negative margins (margin ≥1 mm).
From postoperative day 0 up to 15 weeks postoperatively.

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Peripheral Blood Immune Landscape
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

Flow cytometry analysis is performed on peripheral blood samples.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Peripheral Blood Transcriptomics
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

RNA sequencing is performed on peripheral blood samples.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Peripheral Blood Immune Receptor Repertoire
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

TCR sequencing is performed on peripheral blood samples.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Serum Metabolomics
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

The wide arrays of metabolites in peripheral blood samples are analyzed qualitatively and quantitatively.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Serum Cytokine Analysis
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

The wide arrays of cytokines in peripheral blood samples are analyzed qualitatively and quantitatively.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Tissue Transcriptomics
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

RNA sequencing is performed on tissue samples.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Tissue Immune Receptor Repertoire
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

TCR sequencing is performed on tissue samples.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Tissue Immunohistochemistry
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

Multi-marker fluorescent immunohistochemistry is performed on tissue samples.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Changes of Intestinal Flora
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

Fecal samples are analyzed by metagenomics sequencing.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.
Fecal Metabolomics
Délai: Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

The wide arrays of metabolites in fecal samples are analyzed qualitatively and quantitatively.
Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Chuangzhen Chen

Collaborateurs

BeOne Medicines

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

5 décembre 2025

Achèvement primaire (Estimé)

30 octobre 2029

Achèvement de l'étude (Estimé)

30 octobre 2029

Dates d'inscription aux études

Première soumission

1 décembre 2025

Première soumission répondant aux critères de contrôle qualité

4 janvier 2026

Première publication (Réel)

14 janvier 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

5 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

30 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • SUMC-ILDR03

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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