Esophageal Squamous Cell Carcinoma by AJCC V8 Stage, Resectable Esophageal Cancer
Conditions
Keywords
Esophageal squamous cell carcinoma, Neoadjuvant chemoradiotherapy, Toripalimab, Pathologic complete response
Brief summary
Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal cancer (EC). However, only 20% to 40% of EC patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with neoadjuvant CRT in locally advanced esophageal squamous cell carcinoma (ESCC).
Interventions
DRUGToripalimab
Patients received toripalimab 240 mg IVDRIP on days 1 and 22 during neoadjuvant radiotherapy.
Patients received 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 during neoadjuvant radiotherapy.
RADIATIONIntensity-modulated radiotherapy
All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 44 Gy in 20 fractions over 4 weeks.
PROCEDUREEsophagectomy
A transthoracic (Ivor-Lewis) esophagectomy is performed 6-8 weeks after CRT completion.
Sponsors
Jianhua Fu
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. A histopathological diagnosis of resectable thoracic esophageal squamous cell carcinoma with a pre-treatment clinical stage of T1-4aN1-3M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system; 2. Patients who are anti-tumor treatment-naive; 3. Estimated life expectancy \>6 months 4. Aged 18 to 70 years old of either gender 5. 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; 6. PS score of 0-1; 7. 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. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin; 3. Patients who have a preexisting or coexisting bleeding disorder; 4. Other uncontrollable inoperable patients; 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 ≥ 3 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 or surgery 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response rate | Three working days after surgery | The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-year disease-free survival | From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months. | The 2-year disease-free survival of the whole group |
| Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0 | From the enrollment to the date of surgery | The neoadjuvant treatment-related adverse events |
| 2-year overall survival | From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months | The 2-year overall survival of the whole group |
| Perioperative complication rate | From date of surgery to 30 days later | The perioperative complication rate of esophagectomy |
| Perioperative mortality | From date of surgery to 30 days later | The perioperative mortality of esophagectomy |
| R0 resection rate | Three working days after surgery | The R0 resection rate of esophagectomy |
Countries
China
Contacts
Primary ContactMian Xi, MD
Backup ContactHong Yang, MD
Outcome results
None listed