A Phase II Trial of Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Esophageal Squamous Cell Carcinoma by AJCC V8 Stage
- Sponsor
- Jianhua Fu
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Pathologic complete response rate
- Last Updated
- 6 years ago
Overview
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).
Investigators
Jianhua Fu
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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;
- •Patients who are anti-tumor treatment-naive;
- •Estimated life expectancy \>6 months
- •Aged 18 to 70 years old of either gender
- •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;
- •PS score of 0-1;
- •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.);
- •Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
- •Patients who have a preexisting or coexisting bleeding disorder;
- •Other uncontrollable inoperable patients;
- •Female patients who are pregnant or lactating;
- •Inability to provide informed consent due to psychological, familial, social and other factors;
- •Presence of CTC grade ≥ 3 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 or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
Arms & Interventions
Toripalimab group
All patients will receive standard fractionation radiation therapy (RT) scheme: 44Gy in 20 fractions over 4 weeks, concurrently with 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 and 2 cycles of toripalimab 240 mg on days 1, 22. Esophagectomy is performed 6-8 weeks after CRT completion.
Intervention: Toripalimab
Toripalimab group
All patients will receive standard fractionation radiation therapy (RT) scheme: 44Gy in 20 fractions over 4 weeks, concurrently with 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 and 2 cycles of toripalimab 240 mg on days 1, 22. Esophagectomy is performed 6-8 weeks after CRT completion.
Intervention: Paclitaxel/cisplatin
Toripalimab group
All patients will receive standard fractionation radiation therapy (RT) scheme: 44Gy in 20 fractions over 4 weeks, concurrently with 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 and 2 cycles of toripalimab 240 mg on days 1, 22. Esophagectomy is performed 6-8 weeks after CRT completion.
Intervention: Intensity-modulated radiotherapy
Toripalimab group
All patients will receive standard fractionation radiation therapy (RT) scheme: 44Gy in 20 fractions over 4 weeks, concurrently with 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 and 2 cycles of toripalimab 240 mg on days 1, 22. Esophagectomy is performed 6-8 weeks after CRT completion.
Intervention: Esophagectomy
Outcomes
Primary Outcomes
Pathologic complete response rate
Time Frame: Three working days after surgery
The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.
Secondary Outcomes
- Perioperative complication rate(From date of surgery to 30 days later)
- 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)
- R0 resection rate(Three working days after surgery)
- Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0(From the enrollment to the date of surgery)
- 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.)
- Perioperative mortality(From date of surgery to 30 days later)