RECRUITINGPhase 2 / Phase 3INTERVENTIONAL

Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma

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

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 - platelet count at least 100 × 109/L - blood count (hemoglobin) at least 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 willing to sign a consent form Who Should NOT Join This Trial: - 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 conditions (where your immune system attacks your own body) requiring systemic treatment within 2 years - Previous weakened immune system 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 Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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

Treatments Being Tested

DRUG

Chemotherapy

carboplatin plus nab-paclitaxel

DRUG

Immunotherapy (Pembrolizumab)

Pembrolizumab

RADIATION

radiotherapy

40-45Gy/20fx，5 times a week

Locations (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China