Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma (ONTRESCC)

Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II Clinical Study

Our previous study, a single-center, prospective, single-arm Phase II study (Keypoint001) has demonstrated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in locally advanced (cT3-4N+M0) esophageal squamous cell carcinoma. The results show that the pathological complete response rate (pCR) reaches 35%, and the major pathological response rate is over 70%, which is much higher than that of patients receiving chemotherapy alone. Meanwhile, no severe adverse drug reactions have been found in terms of safety, so this treatment regimen is safe and reliable.

However, the cycle of neoadjuvant immunotherapy is still under exploration. Currently, the mainstream research centers adopt a regimen of 2 to 4 cycles. The exploration results of our center have found that most patients' conditions can be further alleviated after 4 cycles compared with after 2 cycles, but there are still a small number of patients with no obvious remission. Therefore, we consider observing whether patients with no obvious remission can achieve a better pathological response rate through further radiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Chemotherapy; Drug: Immunotherapy (Pembrolizumab); Radiation: radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Li Li; Phone Number: +86-10-69152630; Email: Lili4037@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Li Li; Phone Number: +86-10-69152630; Email: Lili4037@pumch.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• male or female
• Age ≥ 18 years old
• Pathological confirmation of esophageal squamous cell carcinoma
• Endoscopic ultrasound, enhanced CT scan of the neck, chest, and abdomen, and esophageal magnetic resonance imaging evaluate as T3 or resectable T4 PET/CT、 Cervical, thoracic, and abdominal enhanced CT evaluation of N0 or N+
• No clear distant metastasis (M0) and only cervical or supraclavicular lymph node metastasis (M1a)
• Tumor longitudinal diameter ≤ 10cm
• The tumor did not involve the dentate line
• ECOG score 0 or 1
• No hematological diseases, no liver or kidney dysfunction
• Absolute neutrophil count ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 11g/L
• ALT ≤ 2 times the upper limit of normal value
• TBil ≤ 1.5 times the upper limit of normal value
• Creatinine clearance rate (Cockroft) ≥ 50ml/min
• Obtain informed consent

Exclusion Criteria:

• T staging evaluation is T1/T2
• PET/CT and other evaluations show distant metastasis (M1)
• Planned pregnancy or patients during pregnancy or lactation
• History of previous chemotherapy, radiation therapy, or immunotherapy
• Previous severe coronary heart disease and heart failure (NYHA grade III/IV)
• Previous pulmonary interstitial fibrosis or severe pulmonary dysfunction that cannot tolerate surgery
• Previous autoimmune disease requiring systemic treatment within 2 years
• Previous immunodeficiency diseases or the need for systemic steroid replacement therapy
• Previous motor or sensory neurotoxic diseases
• Previous mental illness
• Potential diseases that may affect patients' ability to receive planned treatment, such as drug allergies
• Acute infectious diseases requiring systemic treatment
• Previous HIV, HBV, or HCV infections
• Previously received stem cell or solid organ transplantation

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2 cycles chemoimmunotherapy plus surgery; 2 cycles chemoimmunotherapy and surgery	Drug: Chemotherapy; carboplatin plus nab-paclitaxel; Drug: Immunotherapy (Pembrolizumab); Pembrolizumab
Experimental: 4 cycles chemoimmunotherapy plus surgery; 4 cycles chemoimmunotherapy and surgery	Drug: Chemotherapy; carboplatin plus nab-paclitaxel; Drug: Immunotherapy (Pembrolizumab); Pembrolizumab
Experimental: 4 cycles chemoimmunotherapy plus radiotherapy and surgery	Drug: Chemotherapy; carboplatin plus nab-paclitaxel; Drug: Immunotherapy (Pembrolizumab); Pembrolizumab; Radiation: radiotherapy; 40-45Gy/20fx，5 times a week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response	Postoperative pathology according to CAP classification.	After surgery
2-year and 5-year overall survival	overall survival after 2 years and 5 years	2 years and 5 years after therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effect incidence	Adverse effect according to CTCAE and RTOG criteria	1 years after therapy
R0 resection rate		After surgery
postoperative complications	postoperative complications according to Clavien-Dindo classification	After surgery
2-year and 5-year disease-free survival	disease-free survival after 2 years and 5 years	2 years and 5 years after therapy

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Peking University Cancer Hospital & Institute; Military 301 Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: radiotherapy; esophageal squamous cell carcinoma; neoadjuvant chemoimmunotherapy
• 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; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: Keypoint 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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