Neoadjuvant Chemoradiotherapy Plus Surgery vs. Surgery Plus Adjuvant Therapy for ESCC

NCT06775652 | Completed Phase 3 DMC

• 1 other identifier: SCCH-TS1801
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 1

Brief Summary

This phase III randomized clinical trial compared the long-term survival and safety of neoadjuvant chemoradiotherapy (NCRT) followed by surgery versus surgery with adjuvant therapy (AT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Conducted at Sichuan Cancer Hospital, patients were randomly assigned to receive either NCRT (chemotherapy and radiotherapy followed by surgery) or AT (surgery followed by adjuvant therapy based on staging). The primary outcome was overall survival (OS), with secondary outcomes including disease-free survival (DFS), R0 resection rates, and treatment-related toxicity. A total of 245 patients were randomized, and 224 patients were included in the final analysis.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Esophageal squamous cell carcinoma; Neoadjuvant chemoradiotherapy; Adjuvant therapy; Overall survival; Pathological complete response

Outcome Measures

Primary Outcomes (1)

• OS

  Overall survival

  5 years

Secondary Outcomes (4)

• DFS

  5 years

• Adverse Events

  1 years

• R0 resection rate

  1 years

• pathological complete response (pCR) rate

  1 years

Study Arms (2)

NCRT group

EXPERIMENTAL

Drug: Neoadjuvant Chemoradiotherapy; Procedure: Surgery

AT group

ACTIVE COMPARATOR

Procedure: Adjuvant therapy; Procedure: Surgery

Interventions

Neoadjuvant Chemoradiotherapy DRUG

Patients assigned to the NCRT group received intravenous paclitaxel (135 mg/m²) and carboplatin (AUC=2-5) on day 1, administered every three weeks for two cycles. Concurrently, they received intensity-modulated radiotherapy (IMRT) with a total of 20 sessions (CTV 40 Gy, GTV 44 Gy) five days per week. All radiotherapy plans were reviewed by designated radiation oncologists before treatment to ensure quality control. Patients were assessed 4 to 6 weeks after completing NCRT following RECIST 1.1 criteria.

NCRT group

Adjuvant therapy PROCEDURE

Patients in the AT group received surgery as soon as possible after randomization, followed by adjuvant therapy, postoperative adjuvant therapy based on pathological staging, as recommended by the NCCN Clinical Practice Guidelines for Esophageal and Esophagogastric Junction Cancers (2017 V4), starting one month post-surgery with either adjuvant chemotherapy or chemoradiotherapy. The adjuvant chemotherapy regimen was the same as the neoadjuvant chemotherapy regimen, and the adjuvant radiotherapy regimen and dose were administered according to guideline recommendations.

AT group

Surgery PROCEDURE

Surgery

AT group; NCRT group

Eligibility Criteria

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

You may qualify if:

• \. Aged 18 to 75 years, both sexes; 2. Histologically confirmed locally advanced (cT1N+M0 or T2-4aNxM0) thoracic esophageal squamous cell carcinoma (8th UICC-TNM stage); 3. Cervical contrast-enhanced CT showed no suspicious metastatic lymph nodes, and imaging studies confirmed no systemic metastasis; 4. Expected to achieve R0 resection; 5. ECOG performance status 0 to 1; 6. No prior antitumor therapy for esophageal cancer, including chemotherapy, radiotherapy (including planned radiotherapy during the study), hormone therapy, or immunotherapy; 7. Measurable lesions according to RECIST v1.1 criteria; 8. No contraindications for surgery based on preoperative evaluation of organ function; 9. Laboratory test results confirm eligibility:
• Hemoglobin ≥90 g/L;
• White blood cell count ≥ the laboratory lower limit of normal;
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
• Platelet count ≥100×10⁹/L;
• Total bilirubin ≤1.5× upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN;
• Prothrombin time ≤16 seconds and international normalized ratio (INR) ≤1.5× ULN;
• Serum creatinine ≤1.5× ULN or creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula); 10. Women of childbearing potential must agree to use effective contraception (e.g., intrauterine devices, oral contraceptives, or condoms) during the study medication period and for 60 days after the last dose, have a negative serum pregnancy test within 7 days prior to enrollment, and must not be lactating; 11. Men must agree to use effective contraception during the study medication period and for 60 days after the last dose; 12. Participants must understand and sign the informed consent form.

You may not qualify if:

• \. History of Other Malignancies: 1.1. Patients who have had malignancies other than esophageal cancer.
• \. Bleeding Tendency and Coagulation Disorders: 2.1. Gastrointestinal bleeding within 6 months prior to randomization. 2.2. Coagulation disorders at the time of enrollment. 2.3. Patients receiving thrombolysis or anticoagulant therapy.
• \. Cardiovascular and Cerebrovascular Diseases: 3.1. The following conditions within 12 months prior to randomization:
• Congestive heart failure classified as NYHA class II or higher.
• Unstable angina, myocardial infarction, or poorly controlled arrhythmias.
• Cerebrovascular accidents. 3.2. Left ventricular ejection fraction (LVEF) \<50% on echocardiography. 3.3. Corrected QT interval (QTc) \>480 ms (calculated using the Fridericia formula; if QTc is abnormal, three consecutive tests should be conducted at 2-minute intervals, and the average value used).
• Medically difficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg) based on the average of at least two measurements.
• History of hypertensive crises or hypertensive encephalopathy.
• \. Respiratory Diseases: 4.1. History of interstitial lung disease or pneumonia requiring steroid treatment at enrollment.
• Active tuberculosis at the time of randomization or anti-tuberculosis treatment within 1 year prior to randomization.
• Asthma requiring intermittent bronchodilators or other medical interventions at randomization.
• \. Infectious and Inflammatory Diseases: 5.1. Patients with active hepatitis B must receive effective treatment before enrollment.
• For patients positive for HCV antibodies, HCV-RNA testing should exclude those with HCV-RNA \>10³ copies/mL.
• Co-infection with HIV.
• \. Surgery-Related Risks: 6.1. Severe unhealed wounds, active ulcers, or untreated fractures at the time of randomization.

Sponsors & Collaborators

• Yongtao Han: lead

Study Sites (1)

Sichuan Cancer Hospital and Institute

Chengdu, Sichuan, 610041, China

Location

Related Publications (1)

• He W, Li Z, Xie Q, Han Y, Peng L, Wang C, Wang K, Liu G, Li H, Zhou Q, Li J, Zhang H, Xiao W, Fang Q, Miao Y, Leng X. Long-Term Survival Outcomes of NCRT With Surgery vs Surgery With Adjuvant Therapy for ESCC: A Single-Center Prospective Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2026 Jan 2;9(1):e2550307. doi: 10.1001/jamanetworkopen.2025.50307.

  PMID: 41490111 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Neoadjuvant Therapy; Chemotherapy, Adjuvant; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator, Professor of Thoracic Surgery

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 15, 2025
• Study Start: January 1, 2018
• Primary Completion: December 31, 2020
• Study Completion: July 31, 2024
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)