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.
1. ≥18 years, any gender
2. 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);
3. ECOG (Eastern Cooperative Oncology Groupper) formance status <= 1. 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;
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；
3. Active infection currently exists . The following conditions occurred within 6 months before randomization: myocardial infarction, cerebrovascular accident, or received gastrointestinal, neurological, cardiopulmonary surgery;
4. History of allergy to chemotherapy drugs or autoimmune disease;
Parallel
Radiation
RadiationIMRT/VMAT technique. Patients receive radiotherapy once daily, 5 days a week for an average of 5 weeks. Radiotherapy is delivered to achieve a dosage of 50Gy in 25 fractions to planning gross tumor volume (PGTV) with involved site included.
TP or PF regimen depended on investigator's choice.
DrugA maximum of six cycles was recommended for chemotherapy. Chemotherapy Regimen 1(TP regimen A): Nab-paclitaxel(Albumin-bound paclitaxel) 110-130mg/ m2，d1，d8; Cisplatin 60-75mg/ m2，d1；Q3W； Chemotherapy Regimen 2 (TP regimen B): Paclitaxel 150-175 mg/m2, d1; Cisplatin 60-75mg/ m2，d1；Q3W； PD-1 inhibitor 200mg, d1, Q3W Chemotherapy Regimen 3 (PF regimen): Capecitabine 800mg/m2, bid, d1-14; Cisplatin 25-30mg/m2, d1,d2, Q3W.
PD-1 inhibitor
Biological/VaccineCamrelizumab (200mg, d1, Q3W) was continued until disease progression, unacceptable toxicity, death, physician or patient decision to withdraw, non-compliance, or discontinuation for administrative reasons (up to 35 cycles).
Overall survival (OS)
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).
Progression-free survival (PFS)
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.
Objective Response Rate (ORR)
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator.
Acute toxicity Rate
Acute toxicity rate was defined as the frequency of toxicities related to the treatment, which arises within one month after administration, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC Adverse Event 5.0).
Late toxicity rate
Late toxicity rate was defined as the frequency of toxicities related to the treatment, which arises after one month after administration, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC Adverse Event 5.0).
Biomarkers for the predicting of efficacy
To explore the dynamic changes of circulating tumor DNA (the frequency of specific mutations by Next-generation sequencing Methodology) from baseline, before and after radiotherapy.
Click on the lead sponsor to view all of their trials.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Lead sponsor
Peking University Cancer Hospital & Institute
Collaborator
Beijing Cancer Prevention & Treatment Society
Collaborator
Hebei Medical University Fourth Hospital
Collaborator
Tianjin Medical University Cancer Institute and Hospital
Collaborator
Fujian Cancer Hospital
Collaborator
Anyang Tumor Hospital
Collaborator
The First Affiliated Hospital with Nanjing Medical University
Collaborator
Sichuan Cancer Hospital and Research Institute
Collaborator
Tengzhou Central People's Hospital
Collaborator
The First Affiliated Hospital of Xiamen University
Collaborator
The First Affiliated Hospital of Zhengzhou University
Collaborator
First Affiliated Hospital Xi'an Jiaotong University
Collaborator
Second Affiliated Hospital of Xi'an Jiaotong University
Collaborator
Affiliated Hospital of North Sichuan Medical College
Collaborator
Changzhou Cancer Hospital of Soochow University
Collaborator
Henan Cancer Hospital
Collaborator
