Concurrent Chemoradiotherapy for Stage IVB Esophageal Squamous Cell Carcinoma（EC-CRT-003）

Study Overview
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Brief Summary
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Retrospective studies suggested that the addition of thoracic concurrent chemoradiotherapy to systemic chemotherapy improved the survival and quality of life (QOL) of patients with metastatic esophageal squamous cell carcinoma (ESCC). However, no prospective study had been conducted to confirm these findings. Recently, immunotherapy targeting the PD-1/PD-L1 checkpoints combined with chemotherapy had been proved to significantly prolong the survival of those patients compared with chemotherapy alone. Moreover, anti-PD-1 combined with radiotherapy exerts a synergistic anti-tumor effect, which may further improve the combination efficacy. This randomized, phase II study aimed to evaluate the efficacy and safety of the chemotherapy and anti-PD-1 combined with concurrent chemoradiotherapy to primary tumor versus systemic therapy alone in stage IVB ESCC. Of note, non-regional lymph node metastasis only was the stratification factor in the random assignment.

Official Title
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Systemic Therapy Combined With Thoracic Concurrent Chemoradiotherapy Versus Systemic Therapy Alone in Stage IVB Esophageal Squamous Cell Carcinoma: A Prospective Randomized Phase II Study

Conditions
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Metastatic Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Combination Product: Intensity-modulated radiotherapy concurrent with capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group performance status ≤ 2 Histologically confirmed squamous cell carcinoma of the esophagus; Diagnosed with stage IVB disease (according to UICC TNM version 8); Received 4 to 6 cycles of standard chemotherapy (fluoropyrimidine or taxane-based platinum doublet chemotherapy) and anti-PD1 treatment, and no progression disease was confirmed; Estimated life expectancy >4 months; The function of important organs meet the following requirements: a. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 100×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate >60 mL/min; Ability to understand the study and sign informed consent. Exclusion Criteria: Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment; Patients with intracranial metastasis disease at diagnosis; History of thoracic irradiation; Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum; Patients who have a preexisting esophagomediastinal fistula and/or esophagotracheal fistula; A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia. Inability to provide informed consent due to psychological, familial, social, and other factors; Female patients who are pregnant or during lactation; Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation; A history of interstitial lung disease or non-infectious pneumonia; Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Concurrent Chemoradiotherapy group<br>After completion of 4 to 6 cycles of standard chemotherapy and anti-PD1, all patients will receive thoracic radiation therapy (RT) in the following scheme: 45 to 50.4Gy in 25 to 28 fractions, concurrently with 2 cycles of capecitabine tablets (825mg/m2) for two weeks, and then followed by a maintenance treatment phase of anti-PD1 every 3 weeks. | Combination Product: Intensity-modulated radiotherapy concurrent with capecitabine<br>* All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 45 to 50.4Gy in 25 to 28 fractions, concurrently with 2 cycles of capecitabine tablets (825mg/m2) for two weeks.<br>|
| No Intervention: Control group<br>After completion of 4 to 6 cycles of standard chemotherapy and anti-PD1, patients will receive the maintenance treatment with anti-PD1 every 3 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year progression-free survival | The 1-year progression-free survival of each group | From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year overall survival | The 1-year overall survival of the each group | From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 12 months | 
| ORR | Overall response rate | 3 months after chemoradiotherapy (plus or minus 14 days) | 
| Treatment-related adverse events | Toxicity of treatment was evaluated according to CTCAE 4.0 | From the start of treatment to 2 year after the completion of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic esophageal squamous cell carcinoma, anti-PD-1, Capecitabine, chemoradiotherapy