Definitive Proton Radiotherapy Combined With Chemotherapy and Immunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase I Clinical Study

NCT07034118 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2025-ky212
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC) is definitive concurrent chemoradiotherapy (CCRT). However, conventional photon-based radiotherapy is associated with excessive radiation exposure to normal tissues and a high incidence of treatment-related toxicities. Proton radiotherapy, one of the major advances in radiation oncology in recent years, offers the dosimetric advantage of reduced radiation to surrounding normal tissues, thereby decreasing the rate of adverse events. Two recent clinical studies have suggested that, compared with conventional photon radiotherapy, proton radiotherapy can significantly reduce the incidence of treatment-related toxicities and potentially improve patient survival outcomes. Immune checkpoint inhibitors (ICIs) have been widely used in both locally advanced and advanced esophageal cancer and have demonstrated promising clinical efficacy. Preliminary results from several ongoing phase III clinical trials indicate that combining ICIs with concurrent chemoradiotherapy is both safe and effective. Moreover, proton radiotherapy, by minimizing the low-dose radiation exposure to circulating peripheral lymphocytes, may better preserve systemic immune function. Therefore, compared to photon therapy, proton radiotherapy may theoretically enhance the synergistic effect when combined with ICIs, offering a potential survival benefit. Based on this rationale, we propose a phase I clinical trial to investigate the safety and preliminary efficacy of definitive proton chemoradiotherapy combined with immune checkpoint inhibition in patients with locally advanced esophageal squamous cell carcinoma.

Conditions

Esophageal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Toxicity

  The incidence of myelosuppression, radiation-induced pneumonitis and esophagitis, radiation-induecd cardiac injury, etc.

  One year

Study Arms (1)

Pronton radiotherapy with chemoimmunotherapy

EXPERIMENTAL

Pronton radiotherapy with chemoimmunotherapy

Radiation: Proton radiotherapy; Drug: Immune Checkpoint Inhibitors

Interventions

Proton radiotherapy RADIATION

Patients enrolled would receive proton radiotherapy with chemoimmunotherapy.

Pronton radiotherapy with chemoimmunotherapy

Immune Checkpoint Inhibitors DRUG

Patients enrolled would receive proton radiotherapy and chemoimmunotherapy

Pronton radiotherapy with chemoimmunotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years ECOG performance status 0-1 Histologically confirmed esophageal squamous cell carcinoma (ESCC) Stage II-IVA disease (AJCC 8th edition), confirmed via contrast-enhanced CT of the neck, chest, and abdomen, or PET-CT Unresectable by surgical evaluation or patient refusal of surgery No prior oncologic treatment Life expectancy \>6 months Radiotherapy plan meets physical dose constraints Signed informed consent by patient or legal representative

You may not qualify if:

• Age \<18 or \>75 years ECOG \>1 or inability to tolerate treatment Histology other than squamous cell carcinoma Stage I or IVB disease High risk of hemorrhage or fistula, as assessed by imaging and radiation oncologists Previously treated patients Life expectancy \<6 months Contraindications to chemotherapy or immunotherapy Radiotherapy plan fails to meet dose constraints Lack of signed informed consent

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

Study Sites (1)

Anhui Provincial Hospital

Hefei, Anhui, China

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Dong Qian, M.D. & Ph.D.

CONTACT

+8618202269589; qiandong@ustc.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2025
• First Posted: June 24, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)