A Phase II Trial of Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Pathologic complete response rate
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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).
研究组 & 干预措施
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.
干预措施: Toripalimab (Drug)
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.
干预措施: Paclitaxel/cisplatin (Drug)
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.
干预措施: Intensity-modulated radiotherapy (Radiation)
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.
干预措施: Esophagectomy (Procedure)
结局指标
主要结局
Pathologic complete response rate
时间窗: Three working days after surgery
The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.
次要结局
- 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)
研究者
Jianhua Fu
Professor
Sun Yat-sen University