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

NCT07152678 | Recruiting Phase 2

• 1 other identifier: 202505130MIND
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Cancer; Esophageal Squamous Cell Carcinoma

Keywords

Esophageal squamous cell carcinoma; Brachytherapy; Immune checkpoint inhibitor; Nivolumab; Radiotherapy; Locoregional control

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of locoregional failure at 12 months

  The proportion of patients who develop tumor recurrence or persistence in the esophagus or regional lymph nodes, as assessed by central review using endoscopy, CT and/or PET according to RECIST v1.1 and iRECIST criteria.

  12 months from initiation of HDR brachytherapy

Secondary Outcomes (10)

• Overall Response Rate (ORR)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Progression-Free Survival (PFS)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Duration of Response (DoR)

  Up to 24 months

Study Arms (1)

Add-on of intraluminal brachytherapy with applicator

EXPERIMENTAL

Brachytherapy protocol starts within 3 weeks after first cycle of immunotherapy administered (This is "week 1"). High-dose-rate (HDR) 5-6 Gy per fraction is delivered to 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. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy.

Drug: Nivolumab (240 mg); Radiation: Brachytherapy

Interventions

Nivolumab (240 mg) DRUG

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.

Add-on of intraluminal brachytherapy with applicator

Brachytherapy RADIATION

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.

Add-on of intraluminal brachytherapy with applicator

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-85 years, with ECOG performance 0-2.
• Locally-advanced esophageal squamous cell carcinoma with clinical stage III, IVA with biopsy proven.
• Prior treatment with EBRT (40-50.4 Gy in 20-28 fractions) and platinum + fluoropyrimidine chemotherapy, with residual or progressive disease, and deemed inoperable or unable to undergo surgery.
• No prior exposure to ICIs and had received first cycle of nivolumab after CCRT.
• Biopsy proven with PD-L1 \[tumor cell (TC) ≥ 1%\]
• Required at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
• Patients with limited stage IVB disease (e.g., non-visceral lymph node metastasis) may be enrolled if the primary tumor is locally dominant and suitable for brachytherapy, based on investigator's discretion.

You may not qualify if:

• Current or past history of severe hypersensitivity to any other antibody products.
• Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment.
• Patients with active, known or suspected autoimmune disease
• Stenosis of esophageal lumen that cannot performed brachytherapy
• Involvement of tracheal mucosa or bronchial mucosa.
• The distribution of the lesions of interest exceeds 10 cm range.
• The patient is participating in other interventional clinical trials associated with immunotherapy.
• The patient is scheduled to undergo esophagostomy.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital Yunlin Branch

Huwei, Yunlin County, 632, Taiwan

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma

Interventions

Nivolumab; Brachytherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics

Study Officials

• Yen-Ting Liu, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yen-Ting Liu, MD

CONTACT

+886-2-33663366; nickliucool@ntuh.gov.tw

Study Design

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

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 3, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-07

Locations

TW (1)