Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma

NCT ID: NCT06907602

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-12
• Study Completion Date: 2028-12-31

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.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

2 cycles chemoimmunotherapy plus surgery

2 cycles chemoimmunotherapy and surgery

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

carboplatin plus nab-paclitaxel

Immunotherapy (Pembrolizumab)

Intervention Type: DRUG

Pembrolizumab

4 cycles chemoimmunotherapy plus surgery

4 cycles chemoimmunotherapy and surgery

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

carboplatin plus nab-paclitaxel

Immunotherapy (Pembrolizumab)

Intervention Type: DRUG

Pembrolizumab

4 cycles chemoimmunotherapy plus radiotherapy and surgery

4 cycles chemoimmunotherapy plus radiotherapy and surgery

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

carboplatin plus nab-paclitaxel

Immunotherapy (Pembrolizumab)

Intervention Type: DRUG

Pembrolizumab

radiotherapy

Intervention Type: RADIATION

40-45Gy/20fx，5 times a week

Interventions

Chemotherapy

carboplatin plus nab-paclitaxel

Intervention Type: DRUG

Immunotherapy (Pembrolizumab)

Pembrolizumab

Intervention Type: DRUG

radiotherapy

40-45Gy/20fx，5 times a week

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Military 301 Hospital

UNKNOWN

Sponsor Role: collaborator

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Li Li

Role: CONTACT

Lili4037@pumch.cn

+86-10-69152630

Facility Contacts

Li Li

Role: primary

Lili4037@pumch.cn

+86-10-69152630

Other Identifiers

Keypoint 002

Identifier Type: -

Identifier Source: org_study_id