Induction Immuno-chemotherapy and Concurrent Chemoradiotherapy With or Without Apatinib in Unresectable, Locally Advanced Esophageal Squamous Cell Carcinoma: a Open-label, Randomized, Controlled Phase II Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Induction Immunotherapy-Toripalimab
- Conditions
- Esophageal Squamous Cell Carcinoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 170
- Locations
- 1
- Primary Endpoint
- Progression free survival rate
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This is an open-label, randomized, controlled phase II study evaluating induction immuno-chemotherapy and concurrent chemoradiotherapy with or without apatinib in unresectable, locally advanced esophageal squamous cell carcinoma
Detailed Description
This is an open-label, randomized, controlled phase II study evaluating induction immuno-chemotherapy and concurrent chemoradiotherapy with or without apatinib in unresectable, locally advanced esophageal squamous cell carcinoma. In this study, patients are 1:1 randomized to either the study group or the control group. Patients in the study group will receive apatinib during induction immuno-chemotherapy and concurrent chemoradiotherapy. Patients in the control group will receive induction immuno-chemotherapy and concurrent chemoradiotherapy alone.
Investigators
Hui Liu
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Diagnosed with esophageal squamous cell carcinoma through pathological examination or cytological examination;
- •Evaluated as locally advanced esophageal cancer that is unresectable through endoscopic ultrasound, imaging studies including barium swallow, CT scans of the neck, chest, and upper abdomen, MR imaging of the neck and chest, whole-body bone scan, or PET/CT, with staging ranging from T2-4, N0-3, M0-1 (M1 only includes patients with supraclavicular lymph node metastasis);
- •Male or female aged between 18 and 80 years old;
- •No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy;
- •Expected survival of ≥12 weeks;
- •ECOG performance status score of 0 or 1;
- •Organ and bone marrow function meeting the following criteria: forced expiratory volume in 1 second (FEV1) ≥800 ml; absolute neutrophil count ≥1.5×109/L; platelet count ≥100×109/L; hemoglobin ≥90 g/L; serum creatinine clearance calculated according to the Cockcroft-Gault formula ≥50 mL/min (Cockcroft and Gault 1976); serum bilirubin ≤1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase ≤2.5 times ULN;
- •Signed and dated informed consent form is required before any study procedures are performed.
Exclusion Criteria
- •Participating in another clinical study concurrently, unless it is an observational (non-interventional) clinical study;
- •Prior use of any targeted therapy or immunotherapy;
- •Underwent major surgery (excluding vascular access) within 4 weeks before entering the study;
- •Uncontrolled complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, intestinal perforation, intestinal obstruction, active bleeding disorders, or psychiatric illness/social situations that would limit compliance with study requirements or impair the ability to provide written informed consent;
- •Performance status score of 2-4;
- •Any of the following organ and bone marrow dysfunctions: forced expiratory volume in 1 second (FEV1) \<1000ml; absolute neutrophil count \<1.5×109/L; platelet count \<100×109/L; hemoglobin \<90 g/L; serum creatinine clearance calculated according to the Cockcroft-Gault formula \<50 mL/min (Cockcroft and Gault 1976); serum bilirubin \>1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase \>2.5 times ULN;
- •Conditions that may interfere with the assessment of the efficacy or safety of apatinib;
- •Use of immunosuppressive drugs within 28 days before the first infusion of trastuzumab, excluding physiologic doses of inhaled corticosteroids; or systemic corticosteroids ≤10 mg/d of prednisone or equivalent;
- •History of autoimmune diseases within the past 2 years;
- •History of active or inflammatory bowel disease (such as Crohn's disease, ulcerative colitis);
Arms & Interventions
The study group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
Intervention: Induction Immunotherapy-Toripalimab
The study group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
Intervention: Induction Chemotherapy-Albumin-paclitaxel combined with cisplatin
The study group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
Intervention: Radiotherapy
The study group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
Intervention: Apatinib
The study group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
Intervention: Capecitabine
The control group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
Intervention: Induction Immunotherapy-Toripalimab
The control group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
Intervention: Induction Chemotherapy-Albumin-paclitaxel combined with cisplatin
The control group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
Intervention: Radiotherapy
The control group
Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
Intervention: Capecitabine
Outcomes
Primary Outcomes
Progression free survival rate
Time Frame: 1 year
From the first day of treatment to the day of progression or the day of death.
Secondary Outcomes
- Local-regional progression-free survival(1 year)
- Score of Quality of Life Questionnare-Core 30 (The European Organization for Reasearch and Treatment of Cancer)(1 year)
- Distant metastasis-free survival(1 year)
- Overall survival(1 year)
- Objective response rate(1 year)
- Incidence of Treatment-related Adverse Events(1 year)