Radiotherapy Combined With Immunochemotherapy in Metastatic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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SCR-ESCC-01 is a multicenter, randomized, phase II study aiming to investigate the benefit of early involvement of low-dose radiotherapy(LDRT) and conventionally fractionated radiotherapy(CFRT) in the first-line anti-PD-1 based treatment of metastatic ESCC.

Detailed Description
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In metastatic esophageal cancer, radiotherapy is often administered for palliative purposes to alleviate the symptom of dysphagia. Recent studies have shown that the combination of radiotherapy and immunotherapy may have a synergistic effect on treatment outcomes. The study aims to investigate the benefit of LDRT in combination with conventionally fractionated radiotherapy (CFRT) in improving the outcome of metastatic ESCC concurrently treated with first-line immunochemotherapy. The recruited patients will be randomly (1:1) assigned to receive either PD-1 inhibitor plus chemotherapy (paclitaxel and platinum regimen) (arm B) or in combination with LDRT and CFRT (arm A). The primary endpoint is median progression-free survival (PFS).

Official Title
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First-line Anti-PD-1 Therapy Plus Chemotherapy With or Without Radiotherapy in Metastatic Esophageal Squamous Cell Carcinoma: A Phase II Multi-center, Randomized Trial (SCR-ESCC-01)

Conditions
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Esophageal Squamous Cell Carcinoma, Esophageal Cancer, Metastatic Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: LDRT+CFRT
* Drug: Immunotherapy
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18; Metastatic esophageal squamous cell carcinoma (stage IVB, M1) confirmed by pathology; ECOG performance status: 0-1 point; No prior anti-tumor treatment; Adequate hematologic, renal, hepatic, and cardiac functions that meet the requirements for chemotherapy and immunotherapy assessed by investigators. Exclusion Criteria: Non-squamous cell esophageal carcinoma or ESCC mixed with other pathological types of esophageal cancer; Patients who are potentially curable with surgery as assessed by investigators; Pleural metastasis or malignant pleural effusion, pericardial effusion; Any prior anti-tumor therapy for esophageal cancer, i.e., surgery, radiotherapy, chemotherapy, or immunotherapy; High risk of gastrointestinal bleeding, esophageal fistula, or perforation; Patients with Patient-Generated Subjective Globe Assessment (PG-SGA) score≥9; Unstable cardiac diseases or symptoms; History of interstitial pulmonary disease, non-infectious pneumonitis; pulmonary fibrosis, or other uncontrolled acute pulmonary disease; Active autoimmune disease or history of autoimmune disease; Conditions of immunodeficiency or active infection requiring systemic therapy; Pregnant or breastfeeding; Patients with synchronous second primary cancer and a history of malignancy within the past 5 years (excluding completely cured cervical carcinoma in situ or basal cell or squamous cell skin carcinoma).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin+ Low-dose radiotherapy (LDRT) + Conventionally fractionated radiotherapy (CFRT) | Radiation: LDRT+CFRT<br>* LDRT: Primary tumor and all visible metastatic lesions, DT: 2Gy/2fx, d1-2, Q3W × 4 cycles ; CFRT: Primary tumor, DT:40-50Gy/20-25fx, starting from the 5th immunotherapy cycle<br>Drug: Immunotherapy<br>* PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years<br>Drug: Chemotherapy<br>* Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles<br>|
| Active Comparator: Arm B<br>PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin | Drug: Immunotherapy<br>* PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years<br>Drug: Chemotherapy<br>* Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Median overall survival | From date of randomization until the date of death from any cause, assessed up to 36 months | 
| Incidence of Grade III and higher treatment-related adverse events |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, low-dose radiotherapy, Esophageal squamous cell carcinoma, Immunoradiotherapy