PD-1 Inhibitor Plus Chemotherapy With or Without Radiotherapy in Patients With Metastatic Esophageal Cancer

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 3

Conditions: Esophageal Neoplasms

Treatments: Biological: PD-1 inhibitor; Drug: TP or PF regimen depended on investigator's choice.; Radiation: Radiation

Study type: Interventional

Funder types: Other

Identifiers

NCT06086457

BEIR 0

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 436 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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;
• 5.No prior history of thoracic radiation;
• 6.Expected survival is more than 12 weeks;
• 7.Informed consent provided.

Exclusion criteria

• 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;
• 5. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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436 participants in 2 patient groups

PD-1 inhibitor plus chemotherapy arm

Active Comparator group

Description:

Drugs: TP or PF regimen depended on investigator's choice. A maximum of six cycles was recommended for chemotherapy. Biological: PD-1 inhibitor (Camrelizumab).

Treatment:

Drug: TP or PF regimen depended on investigator's choice.

Biological: PD-1 inhibitor

Radiotherapy arm

Experimental group

Description:

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).

Treatment:

Radiation: Radiation

Drug: TP or PF regimen depended on investigator's choice.

Biological: PD-1 inhibitor