Efficacy, Esophageal Squamous Cell Carcinoma, Toxicity
Conditions
Keywords
Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma, Induction immuno-chemotherapy, Concurrent chemoradiotherapy, Apatinib, Survival outcomes, Toxicity
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.
Interventions
DRUGInduction Immunotherapy-Toripalimab
Toripalimab 240mg iv. drip, Q3W, 2 cycles
DRUGInduction Chemotherapy-Albumin-paclitaxel combined with cisplatin
Albumin-paclitaxel 260 mg/m2, administered on day 1, combined with cisplatin 25 mg/m2, administered on day 1,2,3.
RADIATIONRadiotherapy
Thoracic radiotherapy at a total dose of 50Gy was delivered using the intensity modulated radiation therapy technique.
DRUGApatinib
Oral apatinib 250mg once daily during induction therapy and concurrent chemoradiotherapy.
DRUGCapecitabine
Oral capecitabine 1000 mg/m2, twice daily, on days 1-14, every 3 weeks, concurrently with radiotherapy
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival rate | 1 year | From the first day of treatment to the day of progression or the day of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORHui Liu, Professor
Sun yat-sen universtiy cancer center
Outcome results
None listed