Chemoradiotherapy, Esophageal Squamous Cell Carcinoma, Neoadjuvant Immunochemotherapy, Surufatinib, Toripalimab
Conditions
Keywords
Toripalimab, Surufatinib, Neoadjuvant Immunochemotherapy, Chemoradiotherapy, Esophageal Squamous Cell Carcinoma
Brief summary
The combination of surufatinib with neoadjuvant chemo-immunotherapy and definitive concurrent chemoradiotherapy represents a promising new therapeutic strategy that may further improve the prognosis of patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Therefore, we propose to conduct a prospective, single-arm, phase II clinical trial to evaluate the efficacy and safety of this regimen in patients with unresectable, locally advanced ESCC.
Detailed description
This is a prospective, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of surufatinib in combination with neoadjuvant chemo-immunotherapy and concurrent chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma. Patients will first receive two cycles of neoadjuvant therapy consisting of albumin-bound paclitaxel, cisplatin, toripalimab, and surufatinib. This will be followed by definitive concurrent chemoradiotherapy.
Interventions
Albumin-bound paclitaxel 260 mg/m² on day 1, cisplatin 25 mg/m² on days 1-3, and toripalimab 240 mg on day 1 of each 3-week cycle (q3w), for a total of 2 cycles.
Surufatinib 200 mg orally once daily (po, qd) on days 1-14, administered concurrently with immunochemotherapy. During radiotherapy, surufatinib will be administered at the start of each radiotherapy phase.
DRUGConcurrent Chemotherapy
Toripalimab 240 mg on day 1 of each 3-week cycle (q3w), starting one day prior to the initiation of radiotherapy. Weekly administration of albumin-bound paclitaxel 50 mg/m² and cisplatin 25 mg/m² on day 1 during the radiotherapy course.
RADIATIONRadiotherapy
All patients will undergo thoracic intensity-modulated radiotherapy (IMRT), delivered once daily, 5 days per week, at a total prescribed dose of 50 Gy.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC). * Locally advanced, unresectable esophageal cancer assessed by endoscopic ultrasound and imaging studies, including esophagography, contrast-enhanced CT scans of the lower neck, chest, and upper abdomen, MRI of the lower neck and chest, whole-body bone scintigraphy, or PET/CT; staged as T2-4, N0-3, M0-1 (M1 limited to supraclavicular lymph node metastasis). * Male or female patients aged 18 to 80 years. * No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy. * Expected life expectancy of at least 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ and bone marrow function defined as: Forced expiratory volume in one second (FEV1) ≥ 1000 mL; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L; Creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault formula (Cockcroft and Gault, 1976); Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. * Signed and dated informed consent form must be obtained prior to any study-related procedures.
Exclusion criteria
* Participation in another clinical trial simultaneously, except for observational (non-interventional) studies. * Prior use of any targeted therapy. * Major surgery within 4 weeks prior to study entry (excluding vascular access procedures). * Uncontrolled comorbidities, including but not limited to active or ongoing infections, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, intestinal perforation, bowel obstruction, active bleeding disorders, or psychiatric/social conditions that may impair compliance with study requirements or the ability to provide informed consent. * Performance status (PS) score of 2-4. * Presence of any of the following organ or bone marrow dysfunctions: Forced expiratory volume in one second (FEV1) \< 1000 mL; Absolute neutrophil count (ANC) \< 1.5 × 10⁹/L; Platelet count \< 100 × 10⁹/L; Hemoglobin \< 90 g/L; Creatinine clearance \< 50 mL/min calculated by the Cockcroft-Gault formula (Cockcroft and Gault, 1976); Total bilirubin \> 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5 × ULN. * Any condition that may interfere with the assessment of efficacy or safety of surufatinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year progression-free survival rate | 2 years | The 2-year progression-free survival rate refers to the proportion of patients who remain alive without evidence of disease progression at 24 months after initiation of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 2 months after CCRT | The objective response rate refers to the proportion of patients with a measurable reduction in tumor burden, including complete response (CR) and partial response (PR), as defined by standardized criteria such as RECIST (Response Evaluation Criteria in Solid Tumors). |
| Locoregional Progression-Free Survival (LRPFS) | 2 years | LRPFS is defined as the time from the start of treatment to the first occurrence of locoregional disease progression or death from any cause. |
| Distant Metastasis-Free Survival (DMFS) | 2 years | DMFS refers to the time from treatment initiation to the first occurrence of distant metastasis or death from any cause. It reflects the effectiveness of systemic disease control. |
| Median overall survival (OS) | 2 years | The time from the start of treatment to death from any cause. |
| Patient-reported quality of life | 1 year after treatment | Quality of life assessed using the EORTC Quality of Life Core Questionnaire (QLQ-C30). |
| Patient-reported esophageal-specific symptoms | 1 year after treatment | Esophageal-specific symptoms assessed using EORTC QLQ-OES18 questionnaire. |
| Treatment-related adverse events | 1 year after treatment | The assessment of treatment-related adverse events (AEs), including their type, severity, frequency, and impact on patients. |
Countries
China
Contacts
Primary ContactBo Qiu
Backup ContactHui Liu
Outcome results
None listed