Induction Immuno-chemotherapy and Concurrent Chemoradiotherapy With or Without Apatinib in Unresectable, Locally Advanced Esophageal Squamous Cell Carcinoma

Phase 2

Recruiting

• Conditions: Esophageal Squamous Cell Carcinoma; Efficacy; Toxicity
• Interventions: Drug: Induction Immunotherapy-Toripalimab; Drug: Induction Chemotherapy-Albumin-paclitaxel combined with cisplatin; Radiation: Radiotherapy; Drug: Apatinib; Drug: Capecitabine

• Registration Number: NCT06281886
• Lead Sponsor: Sun Yat-sen University

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.

Study Timeline

• Study Start: 2023-12-01
• Status Verified: 2024-02
• Study First Submitted: 2024-02-13
• Study First Submitted QC: 2024-02-20
• Last Update Submitted: 2024-02-20
• Study First Posted: 2024-02-28
• Last Update Posted: 2024-02-28
• Primary Completion: 2026-12-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 170

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);
• History of organ transplantation requiring immunosuppressive therapy;
• Receipt of attenuated live vaccines within 30 days before the study initiation or within 30 days after receiving trastuzumab;
• History of another primary malignancy within 5 years before starting trastuzumab, except adequately treated basal or squamous cell skin cancer or in situ cervical cancer;
• Pregnant or lactating females; or sexually active males or females of reproductive potential not using effective contraception methods.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The study group	Induction Chemotherapy-Albumin-paclitaxel combined with cisplatin	Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
The study group	Capecitabine	Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
The control group	Induction Immunotherapy-Toripalimab	Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
The study group	Induction Immunotherapy-Toripalimab	Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
The study group	Apatinib	Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
The control group	Induction Chemotherapy-Albumin-paclitaxel combined with cisplatin	Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
The control group	Radiotherapy	Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.
The study group	Radiotherapy	Patients are planned to receive 2 cycles of induction immuno-chemotherapy plus apatinib, followed by concurrent chemoradiotherapy plus apatinib.
The control group	Capecitabine	Patients are planned to receive 2 cycles of induction immuno-chemotherapy, followed by concurrent chemoradiotherapy.

Primary Outcome Measures

Name	Time	Method
Progression free survival rate	1 year	From the first day of treatment to the day of progression or the day of death.

Secondary Outcome Measures

Name	Time	Method
Local-regional progression-free survival	1 year	Local-regional progression-free survival refers to the period from the initiation of treatment until the occurrence of progression in the primary site or locoregional lymph node regions.
Score of Quality of Life Questionnare-Core 30 (The European Organization for Reasearch and Treatment of Cancer)	1 year	The evaluation of life quality
Distant metastasis-free survival	1 year	Distant metastasis-free survival refers to the period from the initiation of treatment until the appearance of metastasis in distant organs or tissues.
Overall survival	1 year	It was calculated from the first day of treatment to the day of death.
Objective response rate	1 year	The proportion of patients evaluated as CR or PR
Incidence of Treatment-related Adverse Events	1 year	Adverse effects are graded according to the CTCAE 5.0 version, including multiple organs and tissues, such as gastrointestinal disease and symptom, cardiovascular disease, respiratory diseases and so on.

Trial Locations

Locations (1)

Sun yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China