NCT07152678

Brachytherapy With Radiotherapy and Immunotherapy: Guided HDR Trial in Esophageal Squamous Cell Carcinoma

A Phase II Study of High-Dose-Rate Esophageal Brachytherapy After External Beam Radiotherapy and Nivolumab in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if adding high-dose-rate (HDR) brachytherapy can improve outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who have already received external beam radiotherapy (EBRT), chemotherapy, and the immune therapy drug nivolumab. The main questions it aims to answer are: * Does HDR brachytherapy reduce the chance of the cancer coming back in the esophagus or nearby areas within 12 months? * What side effects or safety issues occur when HDR brachytherapy is given after EBRT, chemotherapy, and nivolumab? Participants will: * Receive 1-2 sessions of HDR brachytherapy delivered through a thin tube placed inside the esophagus, within three weeks after starting nivolumab. * Continue nivolumab and be monitored with regular follow-up visits, imaging tests, and blood samples to check treatment response and safety.

Detailed description

This is a single-arm, phase II clinical trial designed to evaluate the efficacy and safety of high-dose-rate (HDR) esophageal brachytherapy in combination with external beam radiotherapy (EBRT), chemotherapy, and immune checkpoint inhibition with nivolumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Eligible patients include those with stage III-IVB ESCC who have previously received EBRT with concurrent platinum-fluoropyrimidine chemotherapy and who have initiated nivolumab therapy. HDR brachytherapy (5-12 Gy in 1-2 fractions) will be administered within three weeks following the start of nivolumab. The primary endpoint is the 12-month cumulative incidence of locoregional failure. Secondary endpoints include overall survival, progression-free survival, overall response rate, disease control rate, safety and tolerability, tube-dependence-free survival, tumor-infiltrating lymphocyte density, and circulating tumor DNA dynamics. The rationale for this trial is that HDR brachytherapy offers precise dose escalation directly to the esophageal tumor, which may improve locoregional control beyond EBRT alone. In addition, the combination of localized high-dose irradiation with systemic immune checkpoint inhibition has the potential to enhance antitumor immunity, thereby improving clinical outcomes in this high-risk population.

Conditions

• Esophageal Cancer
• Esophageal Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Nivolumab (240 mg)	After the first cycle of nivolumab administered in the screening phase (1st cycle), nivolumab in the study phase was administered intravenously over 30 minutes at a dose of 240 mg every 2 weeks for at least 2 doses, with 1 cycle after to first brachytherapy (2nd cycle), and 1 more cycle after to second brachytherapy (3rd cycle) if feasible. (each cycle was 2 weeks), until disease progression assessed by the investigator per RECIST version 1.1, or unacceptable toxicity.
RADIATION	Brachytherapy	Brachytherapy protocol starts within 3 weeks after first cycle of nivolumab was administered. After brachytherapy applicator placement, CT simulation scan(s) with dummy source in place will be done for further planning procedure, including adjustment of the applicator and 3D treatment planning. High-dose-rate (HDR) 5-Gy per fraction is delivered to the gross tumor volume (GTV) of esophageal tumor(s), second treatment if applicable will be finished within 2 weeks after the first fraction, a total of 5-12 Gy in 1-2 fractions will be delivered. GTV coverage D90 should equal 100% of prescription. Efforts should be made to spare the adjacent normal organ and to avoid hot spot on normal esophageal mucosa. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy.

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-09-01
• Completion: 2028-09-01
• First posted: 2025-09-03
• Last updated: 2025-09-03

Locations

1 site across 1 country: Taiwan