Low-Dose Involved-Field Radiotherapy Plus Immunochemotherapy for ESCC

Low-Dose Involved-Field Radiotherapy Combined with Immunochemotherapy for Locally Advanced, Unresectable Esophageal Squamous Cell Carcinoma: a Prospective, Single-Arm, Phase II Study.

The aim of this clinical trial is to evaluate whether low-dose involved-field radiotherapy combined with immunochemotherapy can reduce treatment-related adverse effects, enhance progression-free survival (PFS), and improve overall survival (OS) in patients with locally advanced, unresectable esophageal squamous cell carcinoma.

The key questions this study seeks to address are:

• Can low-dose involved-field radiotherapy combined with immunochemotherapy reduce treatment-related adverse effects?
• Does this combined approach improve PFS and OS in these patients?

Participants in the study will:

• Undergo an endoscopy at West China Hospital to confirm their diagnosis.
• Receive a treatment regimen that includes low-dose radiotherapy at 45.0 Gy in 1.8 Gy per fraction over 25 fractions, alongside immunochemotherapy, with three cycles of chemotherapy administered every 3 weeks.
• After completing the full treatment regimen, participants will undergo regular follow-up visits and monitoring by healthcare professionals.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma (ESCC); Immunotherapy
• Intervention / Treatment: Radiation: low-dose involved-field radiotherapy combined with immunochemotherapy

Detailed Description

This is a single-arm, single-center, prospective clinical study aimed at evaluating the efficacy and safety of low-dose involved-field radiotherapy combined with immunochemotherapy in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC). The study will enroll subjects with pathologically confirmed ESCC (via histology or cytology), clinically staged as cT1-4aN+M0, who are deemed unsuitable for surgical intervention by the investigators or have declined surgical treatment.

Initially, patients will receive one cycle of induction immunochemotherapy consisting of paclitaxel or nab-paclitaxel plus carboplatin, in combination with camrelizumab administered at 200 mg intravenously every three weeks. On the first day of the second chemotherapy cycle, low-dose involved-field radiotherapy will commence. The radiotherapy protocol involves a total dose of 45.0 Gy delivered in 25 fractions of 1.8 Gy each (45.0 Gy/1.8 Gy per fraction over 25 fractions). The clinical target volume (CTV) is defined by extending the gross tumor volume (GTV) 3 cm superiorly and inferiorly, and 0.5 cm anteriorly, posteriorly, and laterally; for involved lymph nodes (GTVn), a 0.5 cm margin is added in all directions.

Following disease stabilization, patients will continue with maintenance therapy using camrelizumab monotherapy for up to one year or until disease progression, as assessed by RECIST 1.1 criteria, or the emergence of intolerable adverse effects. Upon completion of treatment, subjects will undergo routine follow-up according to standard care protocols to document survival status and long-term adverse reactions.

The study utilizes a historical control one-year progression-free survival (PFS) rate of 34% from definitive chemoradiotherapy in locally advanced ESCC. It is hypothesized that the combination of camrelizumab with dual-agent chemotherapy (paclitaxel or nab-paclitaxel plus carboplatin) and sequential low-dose involved-field radiotherapy will improve the 12-month PFS rate to 52%. Based on a two-sided significance level (α) of 0.05 and a power (1-β) of 80%, the required sample size is calculated to be 37 patients. Accounting for a 10% dropout rate, a total of 41 patients will be enrolled in the study.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: zhenyu ding, MD; Phone Number: +86 028-854-22562; Email: dingzhenyu@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: zhenyu ding, MD; Phone Number: 18980601957; Email: dingzhenyu@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80 years
• Patients with locally advanced, unresectable ESCC who have received radical treatment (radical chemoradiotherapy or radical radiochemotherapy), including:

Cervical esophagus involvement, T4 stage, supraclavicular lymph node metastasis, or inability to tolerate or refusal of surgery due to personal reasons; Failure of neoadjuvant or conversion therapy;Unresectable local recurrence after surgery (with measurable target lesions)

• No evidence of tumor recurrence or metastasis on follow-up examination 2-3 weeks after radical treatment
• Ability to provide fresh tumor tissue specimens (baseline)
• Normal function of major organs
• Performance Status (PS) score ≤ 1
• Patients of childbearing potential must agree to use contraception.
• Voluntary participation with signed informed consent

Exclusion Criteria:

• History of fistula formation due to primary tumor invasion
• High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation.
• Poor nutritional status
• Previous immune-related adverse events during prior radical treatment, including grade ≥3 immune-related pneumonitis, myocarditis, etc
• Presence of symptoms or signs of interstitial disease
• Patients with any severe and/or uncontrolled medical condition
• Presence of concurrent malignancies
• Presence of other autoimmune diseases or long-term use of immunosuppressants or corticosteroids.
• Patients who are difficult to communicate with or are unlikely to comply with long-term follow-up.
• Any other conditions that the investigator deems unsuitable for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low-dose involved-field radiotherapy combined with immunochemotherapy	Radiation: low-dose involved-field radiotherapy combined with immunochemotherapy; low-dose involved-field radiotherapy combined with immunochemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of low-dose involved-field radiotherapy combined with immunochemotherapy	This study will collected any adverse medical events that occurred during the study drug treatment, and the treatment-related adverse events as assessed by" CTCAE v5.0".	12months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of low-dose involved-field radiotherapy combined with immunochemotherapy	The 1-year Progression-free survival (PFS) rate will be evaluated as the primary endpoint using RECIST 1.1 criteria.	12months
The efficacy of low-dose involved-field radiotherapy combined with immunochemotherapy	Evaluate objective response rate (ORR) using the RECIST 1.1 criteria	12months
The efficacy of low-dose involved-field radiotherapy combined with immunochemotherapy	Using the RECIST1.1 tumor evaluation criteria for efficacy evaluation, evaluate overall survival (OS)	24months

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Principal Investigator: zhenyu ding, MD, West China Hospital, Sichuan University, China

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 27, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; Radiotherapy; Esophageal Squamous Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: HX-LION Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No