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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma

Treatments: Drug: Immunotherapy (Pembrolizumab); Drug: Chemotherapy; Radiation: radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06907602

Keypoint 002

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

2 cycles chemoimmunotherapy plus surgery

Experimental group

Description:

2 cycles chemoimmunotherapy and surgery

Treatment:

Drug: Chemotherapy

Drug: Immunotherapy (Pembrolizumab)

4 cycles chemoimmunotherapy plus surgery

Experimental group

Description:

4 cycles chemoimmunotherapy and surgery

Treatment:

Drug: Chemotherapy

Drug: Immunotherapy (Pembrolizumab)

4 cycles chemoimmunotherapy plus radiotherapy and surgery

Experimental group

Description:

4 cycles chemoimmunotherapy plus radiotherapy and surgery

Treatment:

Radiation: radiotherapy

Drug: Chemotherapy

Drug: Immunotherapy (Pembrolizumab)