Combination of Cadonilimab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-006)

• Status: Recruiting
• Trial end date: 2027-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer. However, as high as more than 40% of patients with esophageal cancer experienced locoregional recurrence after definitive CRT. Immune checkpoint inhibitors targeting PD-1/PD-L1 and/or CTLA-4 have shown substantial clinical benefits in advanced esophageal cancer. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in esophageal cancer. The aim of this study was to evaluate the efficacy and safety of cadonilimab (a bispecific PD-1/CTLA-4 antibody) combined with induction chemotherapy followed by definitive radiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Treatments: Cisplatin; Paclitaxel

Criteria

Inclusion Criteria:

1. Histologically confirmed squamous cell carcinoma of the esophagus;

2. Locally advanced, and absence of distant metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan, stage II-IVA (according to UICC TNM version 8);

3. Not suitable for surgery (either for medical reasons or patient's choice);

4. Age at diagnosis 18 to 75 years;

5. No prior cancer therapy;

6. Estimated life expectancy >6 months;

7. Eastern Cooperative Oncology Group performance status ≤ 2

8. No history of concomitant or previous malignancy;

9. 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;

10. Ability to understand the study and sign informed consent.

Exclusion Criteria:

1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);

2. Patients with distant metastasis disease or esophageal fistula at diagnosis;

3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin;

4. Patients who have a preexisting or coexisting bleeding disorder;

5. Female patients who are pregnant or lactating;

6. Inability to provide informed consent due to psychological, familial, social and other factors;

7. Presence of CTC grade ≥2 peripheral neuropathy;

8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer

9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;

10. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.

11. 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;

12. A history of interstitial lung disease or non-infectious pneumonia;

13. 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;

14. 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).