Systemic Therapy Combined With Thoracic Concurrent Chemoradiotherapy Versus Systemic Therapy Alone in Stage IVB Esophageal Squamous Cell Carcinoma: A Prospective Randomized Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- 1-year progression-free survival
研究概览
简要总结
Retrospective studies suggested that the addition of thoracic concurrent chemoradiotherapy to systemic chemotherapy improved the survival and quality of life (QOL) of patients with metastatic esophageal squamous cell carcinoma (ESCC). However, no prospective study had been conducted to confirm these findings. Recently, immunotherapy targeting the PD-1/PD-L1 checkpoints combined with chemotherapy had been proved to significantly prolong the survival of those patients compared with chemotherapy alone. Moreover, anti-PD-1 combined with radiotherapy exerts a synergistic anti-tumor effect, which may further improve the combination efficacy. This randomized, phase II study aimed to evaluate the efficacy and safety of the chemotherapy and anti-PD-1 combined with concurrent chemoradiotherapy to primary tumor versus systemic therapy alone in stage IVB ESCC. Of note, non-regional lymph node metastasis only was the stratification factor in the random assignment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Eastern Cooperative Oncology Group performance status ≤ 2
- •Histologically confirmed squamous cell carcinoma of the esophagus;
- •Diagnosed with stage IVB disease (according to UICC TNM version 8);
- •Received 4 to 6 cycles of standard chemotherapy (fluoropyrimidine or taxane-based platinum doublet chemotherapy) and anti-PD1 treatment, and no progression disease was confirmed;
- •Estimated life expectancy >4 months;
- •The function of important organs meet 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.
排除标准
- •Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment;
- •Patients with intracranial metastasis disease at diagnosis;
- •History of thoracic irradiation;
- •Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum;
- •Patients who have a preexisting esophagomediastinal fistula and/or esophagotracheal fistula;
- •A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
- •Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia.
- •Inability to provide informed consent due to psychological, familial, social, and other factors;
- •Female patients who are pregnant or during lactation;
- •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;
- •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).
结局指标
主要结局
1-year progression-free survival
时间窗: From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 12 months
The 1-year progression-free survival of each group
次要结局
- 1-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 12 months)
- ORR(3 months after chemoradiotherapy (plus or minus 14 days))
- Treatment-related adverse events(From the start of treatment to 2 year after the completion of treatment)
研究者
Mian XI
principal investigator
Sun Yat-sen University