Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Radioterapia de Baixa Dose Intestinal mais Imunoquimioterapia para Conversão de Carcinoma de Células Escamosas Esofágicas Marginalmente Ressecável/Não Ressecável (ILDR-03)

30 de setembro de 2026 atualizado por: Chuangzhen Chen

Eficácia e Segurança da Combinação de Radioterapia Intestinal de Baixa Dose mais Tislelizumab e Quimioterapia para Conversão de Carcinoma de Células Escamosas do Esófago Borderline Resectável/Não Resectável

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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Estimado)

39

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • China
    • Guangdong
      • Shantou, Guangdong, China, 515031
        • Recrutamento
        • Cancer Hospital, Shantou University Medical College
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 75 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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
Radiação: 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.

Medicamento: PD-1/PD-L1 inhibitors

3 cycles of tislelizumab（200 mg D1 q3w）

Medicamento: Chemotherapy

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

Procedimento: Surgery

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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
1-Year Progression-Free Survival Rate (1y-PFSR)
Prazo: 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.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Pathological Complete Response (pCR) Rate
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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.

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Peripheral Blood Immune Landscape
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Chuangzhen Chen

Colaboradores

BeOne Medicines

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

5 de dezembro de 2025

Conclusão Primária (Estimado)

30 de outubro de 2029

Conclusão do estudo (Estimado)

30 de outubro de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

1 de dezembro de 2025

Enviado pela primeira vez que atendeu aos critérios de CQ

4 de janeiro de 2026

Primeira postagem (Real)

14 de janeiro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

5 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

30 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • SUMC-ILDR03

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever