Clinical trial NCT06281886: Induction Immuno-chemotherapy and Concurrent Chemoradiotherapy With or Without Apatinib in Unresectable, Locally Advanced Esophageal Squamous Cell Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Efficacy
Toxicity
Keywords: Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma
Induction immuno-chemotherapy
Concurrent chemoradiotherapy
Apatinib
Survival outcomes
Toxicity
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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);
* 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.

Primary outcomes:
measure: Progression free survival rate
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year
measure: Objective response rate
timeFrame: 1 year
measure: Local-regional progression-free survival
timeFrame: 1 year
measure: Incidence of Treatment-related Adverse Events
timeFrame: 1 year
measure: Score of Quality of Life Questionnare-Core 30 (The European Organization for Reasearch and Treatment of Cancer)
timeFrame: 1 year
measure: Distant metastasis-free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun yat-sen universtiy cancer center
name: Hui Liu, Professor
role: PRINCIPAL_INVESTIGATOR
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