Intestinal Low-Dose Radiotherapy Plus Immunochemotherapy for Conversion of Borderline Resectable/Unresectable Esophageal Squamous Cell Carcinoma

NCT07339488 | Active Not Recruiting Phase 2

• 1 other identifier: SUMC-ILDR03
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

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 43 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.

Conditions

Borderline Resectable Carcinoma; Chemotherapy; Unresectable Cancer; Esophageal Squamous Cell Carcinoma (ESCC); Immune Checkpoint Inhibitor; Radiotherapy; Tislelizumab

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  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.

Secondary Outcomes (8)

• Major Pathological Response (MPR) Rate

  From postoperative day 0 up to 15 weeks postoperatively.

• Objective Response Rate (ORR)

  Baseline, every 6 weeks during conversion therapy, postoperation, every 4 months following the first postoperative assessment with a maximum duration of 12 months.

• Disease Control Rate (DCR)

  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

  Up to 12 months after surgery.

• 1-Year Disease-Free Survival Rate (1y-DFSR)

  Up to 12 months after surgery.

Other Outcomes (10)

• Peripheral Blood Immune Landscape

  Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

• Peripheral Blood Transcriptomics

  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

  Baseline, and at a follow-up time point within 6 weeks after completion of conversion therapy but before surgical resection.

Study Arms (1)

ILDR plus immunochemotherapy plus surgery

EXPERIMENTAL

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; Drug: PD-1/PD-L1 inhibitors; Drug: Chemotherapy; Procedure: Surgery

Interventions

Intestinal Low Dose Radiotherapy-1Gy RADIATION

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

ILDR plus immunochemotherapy plus surgery

PD-1/PD-L1 inhibitors DRUG

3 cycles of tislelizumab（200 mg D1 q3w）

ILDR plus immunochemotherapy plus surgery

Chemotherapy DRUG

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

ILDR plus immunochemotherapy plus surgery

Surgery PROCEDURE

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

ILDR plus immunochemotherapy plus surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily enroll in this study, sign an informed consent form, and demonstrate good compliance.
• Age ≥18 years and ≤75 years; both sexes are eligible.
• ECOG performance status score of 0-1.
• Pathologically confirmed esophageal squamous cell carcinoma (ESCC) prior to surgery.
• Thoracic esophageal cancer.
• Unresectable lesions, defined as: T4 stage; marginally resectable T3 stage (invading other organs, e.g., trachea, bronchus, or aorta not ruled out by imaging); presence or absence of unresectable lymph nodes or metastatic lymph nodes invading adjacent organs; presence or absence of supraclavicular lymph node metastasis; or clinically confirmed unresectable disease by the surgeon.
• No prior history of anti-tumor treatment, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy.
• Baseline laboratory requirements (within 7 days prior to enrollment):
• Hematology:
• Hb≥90 g/L (no transfusion within 14 days)
• NEUT ≥1.5×10⁹/L
• PLT ≥100×10⁹/L
• WBC≥3×10⁹/L
• Biochemistry:
• ALT and AST≤2.5×ULN

You may not qualify if:

• Patients with distant metastases other than supraclavicular lymph node metastases.
• Presence or high risk of esophageal perforation.
• Patients with contraindications to radiotherapy or immune checkpoint inhibitor (ICI) therapy.
• Patients who previously experienced unacceptable toxicity after receiving ICI therapy.
• Patients with a history of thoracoabdominal/pelvic radiotherapy within 6 months prior to enrollment.
• Adverse reactions from prior anti-tumor treatment have not recovered to CTCAE v5.0 grade≤1 (excluding toxicities deemed by the investigator to pose no safety risk, such as fatigue or alopecia).
• Subjects with active, uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment.
• Respiratory depression, airway obstruction, or tissue hypoxia.
• Severe cardiac disease (i.e., NYHA functional class II or higher).
• Markedly abnormal liver or kidney function (i.e., indicators \>3 times the upper limit of normal).
• Active hepatitis B, hepatitis C, HIV, or syphilis.
• Active brain disease or central nervous system/meningeal metastases with significant symptoms, or impaired decision-making capacity.
• Hypersensitivity to drugs included in the trial.
• Drug and/or alcohol abuse.
• Pregnant or lactating women.

Sponsors & Collaborators

• Chuangzhen Chen: lead
• BeOne Medicines: collaborator

Study Sites (1)

Cancer Hospital, Shantou University Medical College

Shantou, Guangdong, 515031, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Immune Checkpoint Inhibitors; Drug Therapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: January 14, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)