Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2

Conditions: Esophageal Neoplasm Metastatic; Esophageal Cancer Stage IVb

Treatments: Radiation: Consolidation Radiation; Biological: PD-1 inhibitor; Drug: TP (Paclitaxel with cisplatin or carboplatin) or PF (Fluoropyrimidine with cisplatin or carboplatin) regimen depended on investigator's choice.; Radiation: Salvage Radiation

Study type: Interventional

Funder types: Other

Identifiers

NCT06084897

BEIR 1

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 II clinical trial to assess whether radiotherapy could further improve the survival of patients with metastatic esophageal cancer responding to PD-1 Inhibitor plus chemotherapy.

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 metastatic EC.

As reported, for the patients with metastatic lung cancer or EC, locoregional radiotherapy could improve survival, especially in those who responding to systemic therapy. 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 those patients with metastatic EC responding to systemic therapy improve local control, relieve the local symptoms, and even improve survival.

Therefore, the investigators intend to conduct a prospective, multicenter phase II trial to assess the efficiency and safety of radiotherapy with chemotherapy and immunotherapy for 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: 120 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 AJCC Cancer Staging Manual, 8th Edition) or recurrent patients with recurrence after radical treatment (radical treatment includes surgery and radiotherapy, but the recurrence site cannot be located in the previous radiotherapy field).
• 3. ECOG performance 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.For patients after definitive or preoperative radiotherapy, no recurrence was in the prior radiation filed;
• 6.Expected survival is more than 12 weeks;
• 7.Informed consent provided;
• 8.With response to 2-4 cycles of the first-line chemotherapy combined with immunotherapy.

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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120 participants in 2 patient groups

Consolidation radiotherapy

Experimental group

Description:

This treatment group will be receive radiotherapy on the basis of standard first-line treatment, after all planned cycles of chemotherapy combined with PD-1 inhibitor completed.

Treatment:

Drug: TP (Paclitaxel with cisplatin or carboplatin) or PF (Fluoropyrimidine with cisplatin or carboplatin) regimen depended on investigator's choice.

Biological: PD-1 inhibitor

Radiation: Consolidation Radiation

Salvage radiotherapy

Experimental group

Description:

This treatment group will be receive salvage radiotherapy on the basis of standard first-line treatment, when disease progressed and salvage radiotherapy is recommended by multidisciplinary team.

Treatment:

Radiation: Salvage Radiation

Drug: TP (Paclitaxel with cisplatin or carboplatin) or PF (Fluoropyrimidine with cisplatin or carboplatin) regimen depended on investigator's choice.

Biological: PD-1 inhibitor