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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Лучевая терапия 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

Первичные конечные точки

• Cumulative incidence of locoregional failure at 12 months [Срок оценки: 12 months from initiation of HDR brachytherapy]

Вторичные конечные точки (10)

• Overall Response Rate (ORR) [Срок оценки: Up to 24 months]
• Overall Survival (OS) [Срок оценки: Up to 24 months]
• Progression-Free Survival (PFS) [Срок оценки: Up to 24 months]
• Disease Control Rate (DCR) [Срок оценки: Up to 24 months]
• Duration of Response (DoR) [Срок оценки: Up to 24 months]
• Cumulative incidence of distant failure [Срок оценки: Up to 24 months]
• Safety and tolerability [Срок оценки: From first study treatment through 90 days after last dose and up to 24 months for late effect]
• Tube-dependence-free survival [Срок оценки: Up to 24 months]
• Circulating tumor DNA (ctDNA) dynamics [Срок оценки: Baseline and up to 24 months]
• Tumor-infiltrating lymphocyte (TIL) density [Срок оценки: Baseline to up to 12 weeks after HDR brachytherapy]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 1 центр

• National Taiwan University Hospital Yunlin Branch — Huwei

Идентификаторы

NCT: NCT07152678 · 202505130MIND

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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