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Intestinale Lage-Dosis Radiotherapie Plus Immunochemotherapie voor Conversie van Grensresectabel/Niet-resectabel Plaveiseleelcarcinoom van de Slokdarm (ILDR-03)

30 september 2026 bijgewerkt door: Chuangzhen Chen

Effectiviteit en veiligheid van de combinatie van intestinale lage dosis radiotherapie plus tislelizumab en chemotherapie voor conversie van borderline-resectabel/niet-resectabel plaveiseleelcarcinoom van de slokdarm

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Geschat)

39

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • China
    • Guangdong
      • Shantou, Guangdong, China, 515031
        • Werving
        • Cancer Hospital, Shantou University Medical College
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 75 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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
Straling: 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.

Geneesmiddel: PD-1/PD-L1 inhibitors

3 cycles of tislelizumab（200 mg D1 q3w）

Geneesmiddel: Chemotherapy

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

Procedure: Surgery

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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
1-Year Progression-Free Survival Rate (1y-PFSR)
Tijdsspanne: 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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Pathological Complete Response (pCR) Rate
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Peripheral Blood Immune Landscape
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Chuangzhen Chen

Medewerkers

BeOne Medicines

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

5 december 2025

Primaire voltooiing (Geschat)

30 oktober 2029

Studie voltooiing (Geschat)

30 oktober 2029

Studieregistratiedata

Eerst ingediend

1 december 2025

Eerst ingediend dat voldeed aan de QC-criteria

4 januari 2026

Eerst geplaatst (Werkelijk)

14 januari 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

5 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

30 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • SUMC-ILDR03

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

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