Guided high‑dose‑rate esophageal brachytherapy with radiotherapy and nivolumab for 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
We will test whether adding a guided high‑dose‑rate (HDR) esophageal brachytherapy session to prior radiotherapy, chemotherapy, and nivolumab helps people with locally advanced esophageal squamous cell carcinoma lower the chance the tumor returns near the esophagus within 12 months.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 85 Years |
| Sex | All |
| Sponsor | National Taiwan University Hospital Academic / other |
| Drugs / interventions | nivolumab, chemotherapy, immunotherapy |
| Locations | 1 site (Huwei, Yunlin County) |
| Trial ID | NCT07152678 on ClinicalTrials.gov |
What this trial studies
This single‑arm Phase II trial enrolls patients with locally advanced esophageal squamous cell carcinoma who previously received external beam radiotherapy with platinum‑fluoropyrimidine chemotherapy and have started nivolumab. Participants receive 1–2 fractions of guided HDR esophageal brachytherapy (5–12 Gy per fraction) within three weeks after starting nivolumab and continue on nivolumab with scheduled follow‑up. The primary endpoint is the 12‑month cumulative incidence of locoregional failure, and secondary endpoints include overall survival, progression‑free survival, response rates, safety, tube‑dependence‑free survival, tumor‑infiltrating lymphocytes, and circulating tumor DNA dynamics. Patients are monitored with clinical visits, imaging, and blood tests to document tumor response and treatment safety.
Who should consider this trial
Good fit: Adults 18–85 with biopsy‑proven locally advanced (stage III–IVA or selected limited IVB) esophageal squamous cell carcinoma, ECOG 0–2, prior EBRT with concurrent platinum‑fluoropyrimidine chemotherapy, started on nivolumab, PD‑L1 TC ≥1%, and with a primary tumor suitable for intraluminal brachytherapy are the intended candidates.
Not a fit: Patients with brain metastases, prior exposure to immune checkpoint inhibitors, severe antibody hypersensitivity, or tumors not amenable to intraluminal brachytherapy are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could improve locoregional tumor control in the esophagus, reduce early local recurrences, and potentially improve survival or reduce feeding‑tube dependence.
How similar studies have performed: Preclinical work and some clinical reports suggest local high‑dose radiation can enhance immune responses and improve control, but combining esophageal HDR brachytherapy with nivolumab is relatively novel and has limited direct clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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. Exclusion Criteria: * 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.
Where this trial is running
Huwei, Yunlin County
- National Taiwan University Hospital Yunlin Branch — Huwei, Yunlin County, Taiwan (Recruiting)
Study contacts
- Principal investigator: Yen-Ting Liu, MD — National Taiwan University Hospital
- Study coordinator: Yen-Ting Liu, MD
- Email: nickliucool@ntuh.gov.tw
- Phone: +886-2-33663366
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.