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

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Esophageal Squamous Cell Carcinoma

Treatments: Combination Product: Intensity-modulated radiotherapy concurrent with capecitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT05512520

2022-FXY-040

Details and patient eligibility

About

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.

Enrollment: 126 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Eastern Cooperative Oncology Group performance status ≤ 2
2. Histologically confirmed squamous cell carcinoma of the esophagus;
3. Diagnosed with stage IVB disease (according to UICC TNM version 8);
4. 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;
5. Estimated life expectancy >4 months;
6. 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;
7. Ability to understand the study and sign informed consent.

Exclusion criteria

1. Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment;
2. Patients with intracranial metastasis disease at diagnosis;
3. History of thoracic irradiation;
4. Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum;
5. Patients who have a preexisting esophagomediastinal fistula and/or esophagotracheal fistula;
6. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
7. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia.
8. Inability to provide informed consent due to psychological, familial, social, and other factors;
9. Female patients who are pregnant or during lactation;
10. 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;
11. A history of interstitial lung disease or non-infectious pneumonia;
12. 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

Concurrent Chemoradiotherapy group

Experimental group

Description:

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.

Treatment:

Combination Product: Intensity-modulated radiotherapy concurrent with capecitabine

Control group

No Intervention group

Description:

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.