Postoperative Radiotherapy Followed by Immunotherapy for Locally Advanced Esophageal Carcinoma

Sponsor

Anhui Provincial Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05937438

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Carcinoma	Drug: Immune Checkpoint Inhibitors	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients enrolled would be randomly assigned to experimental arm (esophagectomy followed by postoperative radiotherapy with immunotherapy) and controlled arm (esophagectomy followed by postoperative radiotherapy).Patients enrolled would be randomly assigned to experimental arm (esophagectomy followed by postoperative radiotherapy with immunotherapy) and controlled arm (esophagectomy followed by postoperative radiotherapy).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 30, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

1-year disease-free survival [1 year]
1-year disease-free survival

Secondary Outcome Measures

Rate of irradiation-induced or immune-induced pneumonitis [1 year]
Rate of irradiation-induced or immune-induced pneumonitis
3-year disease-free survival [3 year]
3-year disease-free survival
3-year overall survival [3 year]
3-year overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Anhui Provincial Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Dong Qian, Professor, Anhui Provincial Hospital

ClinicalTrials.gov Identifier:

NCT05937438

Other Study ID Numbers:

2023-ky 148

First Posted:

Jul 10, 2023

Last Update Posted:

Jul 10, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Carcinoma

Esophageal Neoplasms

Immune Checkpoint Inhibitors

Study Results

No Results Posted as of Jul 10, 2023