Postoperative Radiotherapy Followed by Immunotherapy for Locally Advanced Esophageal Carcinoma

Postoperative Radiotherapy Followed by Immunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II Study

Esophageal squamous cell carcinoma is a common malignancy in China. Although neoadjuvant chemoradiotherapy followed by esophagectomy remains a standard modality for locally advanced esophageal squamous cell carcinoma, esophagectomy followed by postoperative radiotherapy is also prevalent in China. Several retrospective studies demonstrated that postoperative radiotherapy could improve the prognosis of patients. Nevertheless, there still existed approximately 11.5% and 17.2% of total patients developing local-regional relapse and hematological metastasis. The result of Checkmate 577 has shown that postoperative immunotherapy of nivolumab could improve the disease-free survival (median Disease-free Survival 29.7 mos vs. 11.0 mos). Therefore, investigators aimed to implement a pilot study to explore the safety and efficacy of combining postoperative radiotherapy and immunotherapy for patients with locally advanced esophageal squamous cell carcinoma after esophagectomy.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Carcinoma
• Intervention / Treatment: Drug: Immune Checkpoint Inhibitors

Detailed Description

Trial Title: Postoperative radiotherapy followed by immunotherapy for locally advanced esophageal squamous cell carcinoma: A pilot study Trial Objective: To explore the safety and efficacy of combining postoperative radiotherapy and immunotherapy for patients with locally advanced esophageal squamous cell carcinoma after esophagectomy.

Trial Design: To enroll 70 patients with locally advanced esophageal squamous cell carcinoma who would be randomly assigned to experimental arm (esophagectomy followed by postoperative radiotherapy with immunotherapy) and controlled arm (esophagectomy followed by postoperative radiotherapy).

Inclusion Criteria: a. 18-75 years old. b. after esophagectomy. c. confirmation of squamous cell carcinoma by pathological examination. d. pathological staging of pIIb-IVa. e. over 12 lymph nodes dissected during surgery. f. ECOG 0-1. g. signature of inform consent by patients Exclusion Criteria: a. younger than 18 years old or older than 75 years old. b. without esophagectomy. c. non-squamous cell carcinoma. d. pathological staging of pI, IIa, IVb. e. less than 12 lymph nodes dissected during surgery. f. ECOG 2-3 g. no signature of inform consent.

Esophagectomy: Mckeown or Ivor-Lewis surgery

Staging Examination before Postoperative Radiotherapy: a. ECOG scoring. b. PET-CT (preferred), or chest contrast CT, abdominal ultrasonography and bone scan. c. PD-L1 expression level of surgical specimen. d. NRS2002 and PG-SGS scoring.

Postoperative radiotherapy Radiotherapy CT simulation: Intravenous contrast is recommended for CT simulation. Scan thickness should be less than 5 mm. Thermal mask or vacuum bag is recommended.

Delineation of Clinical Tumor Volume (CTV): CTV should involve relative lymphatic drainage area for primary lesion at different site. For cervical and upper-thoracic esophageal squamous cell carcinoma, CTV should involve bilateral supraclavicular (1R), upper and lower paratracheal (2R and 4R), upper and middle paraesophageal (8U and 8M), subcarinal lymphatic drainage area. For middle esophageal squamous cell carcinoma, CTV should involve bilateral supraclavicular (1R), upper and lower paratracheal (2R and 4R), upper, middle and lower paraesophageal (8U, 8M and 8L), subcarinal lymphatic drainage area. For lower esophageal squamous cell carcinoma, CTV should involve middle and lower paraesophageal (8M and 8L), subcarinal lymphatic drainage area.

Production of Planning Tumor Volume (PTV): PTV is produced by a margin of 5 mm added to CTV.

Prescription Dose: 50.4Gy/28f was prescribed to 95% PTV. Dosimetric Limitation: 95% prescription dose should cover 100% PTV and 95% PTV should receive 100% prescription dose. Total Lung: V20<25%, Dmean<13Gy, V5<50%. Spinal Cord: Dmax<45Gy. Heart: V30<40%, Dmean<25Gy. Treatment Implementation: Radiotherapy is implemented every day. Conebeam CT should be utilized per week to confirm set-up error.

Randomization All participants enrolled after postoperative radiotherapy would be randomly assigned to the experimented arm and controlled arm.

Experimental Arm (Immunotherapy Maintenance) Participants enrolled into experimental arm were prescribed to receive immunotherapy maintenance for one year.

Controlled Arm Participants enrolled into controlled arm began to be followed-up after postoperative radiotherapy.

Follow-up: Participants should be follow-up every three months right after the completion of radiotherapy or immunotherapy to 3 years after radiotherapy or immunotherapy. Then follow-up every half year is allowed to 5 years after radiotherapy or immunotherapy. After 5 years, follow-up every year is appropriate. In follow-up, chest CT and abdominal ultrasonography should be implemented.

Primary endpoint: 1-year disease-free survival (RECIST V1.1) Secondary endpoint: Rate of irradiation-induced or immune-induced pneumonitis, 3-year disease-free survival and 3-year overall survival.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dong Qian, M.D.; Phone Number: +86-19156007756; Email: qiandong@ustc.edu.cn
• Study Contact Backup: Name: Dong Qian, M.D.; Phone Number: +8619156007756; Email: qiandong@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provicial Hospital
      • Contact: Xiaoyang Li, M.D.; Phone Number: +8618701851829; Email: drxyl@ustc.edu.cn
      • Principal Investigator: Dong Qian, M.D.
      • Sub-Investigator: Xiaoyang Li, M.D.
      • Contact: Dong Qian, M.D.; Phone Number: +86-19156007756; Email: qiandong@ustc.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-75 years old.
• After esophagectomy.
• Confirmation of squamous cell carcinoma by pathological examination.
• Pathological staging of pIIb-IVa.
• Over 12 lymph nodes dissected during surgery.
• ECOG 0-1.
• Signature of inform consent by patients

Exclusion Criteria:

• Younger than 18 years old or older than 75 years old.
• Without esophagectomy.
• Non-squamous cell carcinoma.
• Pathological staging of pI, IIa, IVb.
• Less than 12 lymph nodes dissected during surgery.
• ECOG 2-3 g. no signature of inform consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Esophagectomy+postoperative radiotherapy+immunotherapy	Drug: Immune Checkpoint Inhibitors; Patients assigned to experimental arm would receive the maintenance treatment of immune checkpoint inhibitor (Tislelizumab or Camrelizumab) after postoperative radiotherapy for one year
Other: Controlled Arm; Esophagectomy+postoperative radiotherapy	Drug: Immune Checkpoint Inhibitors; Patients assigned to experimental arm would receive the maintenance treatment of immune checkpoint inhibitor (Tislelizumab or Camrelizumab) after postoperative radiotherapy for one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year disease-free survival	1-year disease-free survival	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of irradiation-induced or immune-induced pneumonitis	Rate of irradiation-induced or immune-induced pneumonitis	1 year
3-year disease-free survival	3-year disease-free survival	3 year
3-year overall survival	3-year overall survival	3 year

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Dong Qian, M.D., The First Affiliated hospital of USTC

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 25, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 26, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• 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; Carcinoma; Esophageal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2023-ky 148

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