Consolidation of Toripalimab After Chemoradiotherapy in Elderly Esophageal Cancer (EC-CRT-007)

A total of 140 patients with elderly, unresectable, locally advanced ESCC will be stratified according to age (70-80 vs. ≥80) and TNM stage (I/II vs. III/IV) and randomly assigned (1:1) to receive toripalimab as consolidation therapy for up to 12 months (arm A) or not (arm B) after definitive radiotherapy with concurrent S-1.

Inclusion criteria

• Histologically confirmed squamous cell carcinoma of the esophagus;
• Locally advanced, and absence of hematogenous metastasis disease according to UICC TNM version 8;
• Not suitable for surgery (either for medical reasons or patient's choice);
• Age at diagnosis 70 to 85 years;
• No prior cancer therapy;
• Estimated life expectancy >6 months;
• Eastern Cooperative Oncology Group performance status ≤ 2
• No history of concomitant or previous malignancy;
• The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate >60 mL/min;
• Ability to understand the study and sign informed consent.

Exclusion criteria

• Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
• Patients with hematogenous metastasis disease or esophageal fistula at diagnosis;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
• Patients who have a preexisting or coexisting bleeding disorder;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• Presence of CTC grade ≥2 peripheral neuropathy;
• A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
• Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
• A history of interstitial lung disease or non-infectious pneumonia;
• A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).