PD-1 Inhibitor Plus Chemotherapy With or Without Radiotherapy in Patients With Metastatic Esophageal Cancer: A Randomized Multicenter Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 436
- 试验地点
- 1
- 主要终点
- Overall survival (OS)
研究概览
简要总结
The treatment efficacy for stage IVb esophageal cancer has been improved through chemotherapy combined with immunotherapy recently.
On this basis, the investigators intend to conduct a prospective, multicenter phase III clinical trial to assess whether radiotherapy with concurrent chemotherapy and immunotherapy could further improve the survival of patients with metastatic esophageal cancer.
Accompanied tissue samples, blood samples and urine samples will be analyzed by molecular biological detection (Including Whole Exome Sequencing and proteomics) to explore potential biomarkers for predicting outcomes, efficacy and toxicity.
详细描述
Esophageal cancer (EC) is one of the most common carcinomas with high morbidity and mortality worldwide. More than 30% of the patients were stage IV when diagnosed. Fluoropyrimidine plus platinum-based chemotherapy is recommended as first-line treatment for patients with metastatic EC for approximately four decades, however, only minimal improvement has been reached in overall survival (OS).
Recently, immune checkpoint inhibitors have shown effective antitumor activity in patients with unresectable, advanced or metastatic EC. Several randomized trials have demonstrated the PD-1 inhibitor could further improve the OS in patients with advanced esophageal squamous cell carcinoma (ESCC) on the basis of chemotherapy. Chemotherapy combined with immunotherapy has become one of the the standard treatment modality for advanced EC.
As reported, for the patients with metastatic lung cancer or EC, locoregional radiotherapy could improve survival. However, high-level evidence is still needed to assess whether these patients can benefit from local radiotherapy.
The efficacy of immunotherapy combined with chemotherapy is obviously better than that of chemotherapy alone. On this basis, locoregional radiotherapy may help some patients with advanced EC improve local control, relieve the local symptoms and improving the quality of life.
Therefore, the investigators intend to conduct a prospective, multicenter phase III trial to assess the efficiency and safety of radiotherapy with chemotherapy and immunotherapy of patients with metastatic EC. Accompanied tissue samples, blood samples and urine samples will be analyzed by molecular biological detection to explore potential biomarkers for predicting outcomes, efficacy and toxicity.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years, any gender
- •Histologically or cytologically confirmed squamous cell carcinoma of esophageal cancer. The initial clinical stage is IVb (2018 American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition) , with distant metastasis involving no more than 2 organs (lymph node metastasis is counted);
- •ECOG (Eastern Cooperative Oncology Groupper) formance status <=
- •Patients aged 65 years and over need to complete G8 screening or Comprehensive Geriatric Assessment, and the final evaluation is good;
- •4.There was no significant abnormality in laboratory routine indicators such as blood routine and liver and kidney function;
- •5.No prior history of thoracic radiation;
- •6.Expected survival is more than 12 weeks;
- •7.Informed consent provided.
排除标准
- •1.Patients with other cancer history except hypopharyngeal carcinoma in situ, non-malignant skin cancer and cervical carcinoma in situ.
- •2.Received surgery (except ostomy), chemotherapy or other anti-tumor treatment before enrollment；
- •Active infection currently exists . The following conditions occurred within 6 months before randomization: myocardial infarction, cerebrovascular accident, or received gastrointestinal, neurological, cardiopulmonary surgery;
- •History of allergy to chemotherapy drugs or autoimmune disease;
- •Participate in other clinical trials at present or within 4 weeks before enrollment;
- •6.There are factors such as high risk of fistula that radiotherapy cannot be safely carried out as assessed by the radiation oncologist.
研究组 & 干预措施
PD-1 inhibitor plus chemotherapy arm
Drugs: TP or PF regimen depended on investigator's choice. A maximum of six cycles was recommended for chemotherapy.
Biological: PD-1 inhibitor (Camrelizumab).
干预措施: TP or PF regimen depended on investigator's choice. (Drug)
PD-1 inhibitor plus chemotherapy arm
Drugs: TP or PF regimen depended on investigator's choice. A maximum of six cycles was recommended for chemotherapy.
Biological: PD-1 inhibitor (Camrelizumab).
干预措施: PD-1 inhibitor (Biological)
Radiotherapy arm
Radiation: Intensity-modulated Radiation Therapy/Volumetric Modulated Arc Therapy (IMRT/VMAT) technique. Patients will receive radiotherapy between the first and third cycle of chemotherapy.
Drugs: TP or PF regimen depended on investigator's choice. Biological: PD-1 inhibitor (Camrelizumab).
干预措施: Radiation (Radiation)
Radiotherapy arm
Radiation: Intensity-modulated Radiation Therapy/Volumetric Modulated Arc Therapy (IMRT/VMAT) technique. Patients will receive radiotherapy between the first and third cycle of chemotherapy.
Drugs: TP or PF regimen depended on investigator's choice. Biological: PD-1 inhibitor (Camrelizumab).
干预措施: TP or PF regimen depended on investigator's choice. (Drug)
Radiotherapy arm
Radiation: Intensity-modulated Radiation Therapy/Volumetric Modulated Arc Therapy (IMRT/VMAT) technique. Patients will receive radiotherapy between the first and third cycle of chemotherapy.
Drugs: TP or PF regimen depended on investigator's choice. Biological: PD-1 inhibitor (Camrelizumab).
干预措施: PD-1 inhibitor (Biological)
结局指标
主要结局
Overall survival (OS)
时间窗: Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).
Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported for all participants of the Intent-To-Treat (ITT) population (all randomized).
次要结局
- Acute toxicity Rate(One month within the end of one specific treatment.)
- Late toxicity rate(One month after the end of one specific treatment.)
- QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-OES18 Subscale Score in Participants(24 months)
- Objective Response Rate (ORR)(Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).)
- Progression-free survival (PFS)(Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).)
- QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-C30 Subscale Score in Participants(24 months)