Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma

Phase 2

Recruiting

• Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Chemotherapy; Drug: Immunotherapy (Pembrolizumab); Radiation: radiotherapy

• Registration Number: NCT06907602
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-12
• Status Verified: 2025-03
• Study First Submitted: 2025-03-27
• Study First Submitted QC: 2025-03-27
• Last Update Submitted: 2025-03-27
• Study First Posted: 2025-04-02
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2 cycles chemoimmunotherapy plus surgery	Chemotherapy	2 cycles chemoimmunotherapy and surgery
2 cycles chemoimmunotherapy plus surgery	Immunotherapy (Pembrolizumab)	2 cycles chemoimmunotherapy and surgery
4 cycles chemoimmunotherapy plus surgery	Chemotherapy	4 cycles chemoimmunotherapy and surgery
4 cycles chemoimmunotherapy plus surgery	Immunotherapy (Pembrolizumab)	4 cycles chemoimmunotherapy and surgery
4 cycles chemoimmunotherapy plus radiotherapy and surgery	Chemotherapy	4 cycles chemoimmunotherapy plus radiotherapy and surgery
4 cycles chemoimmunotherapy plus radiotherapy and surgery	Immunotherapy (Pembrolizumab)	4 cycles chemoimmunotherapy plus radiotherapy and surgery
4 cycles chemoimmunotherapy plus radiotherapy and surgery	radiotherapy	4 cycles chemoimmunotherapy plus radiotherapy and surgery

Primary Outcome Measures

Name	Time	Method
Pathological response	After surgery	Postoperative pathology according to CAP classification.
2-year and 5-year overall survival	2 years and 5 years after therapy	overall survival after 2 years and 5 years

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China