Clinical trial NCT06478355: Immunotherapy Combined With Chemoradiotherapy for First-line Treatment of Esophageal Squamous Cell Carcinoma（ChinECR）
Official title: Immunotherapy Combined With Chemoradiotherapy for First-line Treatment of Esophageal Squamous Cell Carcinoma:a Real-world Study From China
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: ESCC
Keywords: ESCC
immunotherapy
chemoradiotherapy
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial aims to assess efficacy and safety of immunotherapy combined with chemoradiotherapy for first-line treatment of esophageal squamous cell carcinoma.

Detailed description: Esophageal squamous cell carcinoma is a highly aggressive malignancy, with squamous cell carcinoma accounting for over 90% of esophageal cancer cases in China. According to the American Cancer Society, the 5-year survival rates vary among patients at different stages of esophageal cancer: approximately 50% for early and mid-stage cases, around 26% for locally advanced cases, and only 5% for those with distant metastasis.In recent years, immunotherapy combined with chemotherapy has emerged as the first-line standard treatment for advanced esophageal cancer, and several phase III trials of immunotherapy combined with radiotherapy are currently underway for locally advanced esophageal cancer. Despite being a novel treatment strategy for patients with locally advanced esophageal cancer, there remains a lack of sufficient evidence-based medical data supporting the use of immunotherapy combined with chemoradiotherapy.In recent years, immunotherapy combined with chemotherapy has emerged as the first-line standard treatment for advanced esophageal cancer, and several phase III trials of immunotherapy combined with radiotherapy are currently underway for locally advanced esophageal cancer. Despite being a novel treatment strategy for patients with locally advanced esophageal cancer, there remains a lack of sufficient evidence-based medical data supporting the use of immunotherapy combined with chemoradiotherapy.

Eligibility criteria: Inclusion Criteria:

* Voluntary participation and written signed informed consent;
* Age 18-85 years old, gender is not limited;
* Histologically or cytologically confirmed esophageal squamous cell carcinoma Exclusion Criteria,and patients with suspected brain or bone metastasis at the time of screening should undergo brain MRI or ECT before study enrollment;
* Physical status score ECOG 0-1;
* Weight \&gt; 40 kg;
* Expected survival ≥ 6 months;
* According to RECIST 1.1 guidelines, at least one lesion (not previously receiving radiotherapy) with a maximum diameter ≥ 10 mm as accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline (except lymph nodes, whose short axis must be ≥ 15 mm); And the lesion is suitable for repeated accurate measurement.;
* No previous immunotherapy;
* no serious abnormalities of haematopoietic, cardiac, pulmonary, hepatic; and renal functions and immunodeficiency (Haematology: white blood cells ≥3.5×109/L; neutrophils ≥1.5×109/L; haemoglobin ≥90g/L; platelets

  ≥100×109/L. Liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) ≤2.5 times the upper limit of normal; creatinine ≤1.5 times the upper limit of normal; albumin ≥30 g/L. Coagulation: International Normalised Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (APTT)

  ≤ 1.5 times ULN; if the subject is receiving anticoagulation therapy, PT or INR is acceptable as long as the PT or INR is within the range of the anticoagulant drug formulation. Echocardiographic assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%). Pulmonary function FEV1 ≥70% of % of predicted value and DLCO ≥60% of % of predicted value).
* The female patient has evidence of postmenopausal status, or the urine or serum pregnancy test results of the premenopausal woman are negative. Women who stop menstruating for 12 months without other medical reasons are considered menopausal.

Exclusion Criteria:

* having any active autoimmune disease or a history of autoimmune disease (e.g. interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (which can be included if hormone replacement therapy is effective), etc.), and a history of immunosuppressive drug use within 28 days, with the exception of the use of hormones for the purpose of dealing with toxicity from radiotherapy;
* Previously received or are receiving other PD-1 antibody therapy or other immunotherapy targeting PD-1/PD-L1, or are currently participating in other interventional clinical studies for treatment;
* Have received other anti-tumour therapy (including herbal therapy with anti-tumour effect) within 4 weeks prior to the first dose of the study; have received long-term systemic immunotherapy or hormone therapy (except physiological replacement therapy, e.g., oral thyroxine for hypothyroidism) within 4 weeks prior to the first dose of the study; and have been treated with other experimental drugs or interventional clinical studies within 4 weeks prior to the first dose of the study;
* Patients with uncontrolled clinical cardiac symptoms or disease such as

  (1) NYHA class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
* with congenital or acquired immune function defects (e.g., HIV-infected patients), active hepatitis B (HBV-DNA ≥104 copies/ml) or hepatitis C (hepatitis C antibody-positive with HCV-RNA above the lower limit of detection of the analytical method), or active tuberculosis;
* Have an active infection or unexplained fever \&gt;38.5°C within 2 weeks prior to screening (at the investigator\&#39;s discretion, subjects may be enrolled for fever arising from tumours);
* In the judgement of the investigator, the subject has other factors that may cause him/her to be forced to terminate the study in the middle of the study, e.g., suffering from other serious illnesses (including psychiatric illnesses) that require comorbid treatment, family or social factors that may affect the safety of the subject or the collection of trial data.

Primary outcomes:
measure: Assessment of objective remission rate (ORR) in esophageal squamous cell carcinoma treated with immunotherapy combined with chemoradiotherapy
timeFrame: Treatment with immunotherapy for at least 6 months, or from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Assessment of the incidence of treatment-related adverse events Incidence of Treatment-Emergent Adverse Events
timeFrame: Treatment with immunotherapy for at least 6 months, or from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Secondary outcomes:
measure: Assessment of overall survival (OS) in esophageal squamous cell carcinoma
timeFrame: Treatment with immunotherapy for at least 6 months, or from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Assessment of progression-free survival (PFS) in esophageal squamous cell carcinoma
timeFrame: Treatment with immunotherapy for at least 6 months, or from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Assessment of disease control rate (DCR) in esophageal squamous cell carcinoma
timeFrame: Treatment with immunotherapy for at least 6 months, or from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
state: Hebei
Study officials:
affiliation: Hebei Medical University Fourth Hospital
name: Wenbin Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References: