Clinical trial NCT06122493: Optimization of Treatment Strategy for Unresectable cN3 Esophageal Squamous Cell Carcinoma
Official title: Optimization of Treatment Strategy for Unresectable cN3 Esophageal Squamous Cell Carcinoma: a Phase Ⅱ Single Arm Prospective Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: ESCC
cN3
radiotherapy
chemotherapy
immunotherapy
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2023-11-08
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Chemotherapy includes carboplatin (AUC = 5, d1) and nab-paclitaxel (175 mg/m², day1) every 3 weeks for four cycles. Simultaneously, immunotherapy with tislelizumab (200 mg) is integrated into the treatment plan for these cycles. After the initial four cycles, patients have physical exams and imaging. Those with SD, PR, or CR receive radiotherapy targeting esophageal lesions and positive lymph nodes, with a total dose of 50.4 Gy over 28 fractions. During radiotherapy, two additional cycles of immunotherapy with tislelizumab are given at three-week intervals. After radiotherapy, patients continue with maintenance treatment, taking tislelizumab every three weeks. This maintenance therapy lasts up to a year, or until disease progression or intolerance develops.
Primary purpose: TREATMENT

Brief summary: This study aims to investigate a comprehensive therapeutic approach for patients with unresectable esophageal squamous cell carcinoma, clinically staged as Tany, N3, M0, and who are not candidate for concurrent chemoradiotherapy combined with immunotherapy. The approach entails combining chemotherapy with immune therapy, followed by synchronized radiotherapy during the immune maintenance phase. The primary goal is to mitigate treatment-related side effects and enhance the overall prognosis through the integration of these treatment modalities.

Detailed description: Eligible ESCC patients receive a four-cycle regimen of combined chemotherapy plus immunotherapy. Those without disease progression then get definitive radiotherapy with immune maintenance therapy for up to 12 months.

Eligibility criteria: Inclusion Criteria:

* Esophageal squamous cell carcinoma confirmed through histopathology.
* Distant metastasis excluded by CT, MRI, or PET/CT examinations.
* Locally advanced stage: AJCC/UICC eighth edition staging with any T, N3M0.
* Expected survival time of at least 6 months.
* With an ECOG performance status of 0 to 2. Not accompanied by severe pulmonary hypertension, cardiovascular disease, peripheral vascular disease, severe chronic heart disease, or other comorbidities that could impact radiotherapy progress.
* Adequate function of major organs: Hematopoietic function: Hemoglobin ≥100g/L, platelets ≥90×109/L, white blood cells ≥4×109/L. Exceptions may be considered for patients with ECOG 0-1 who have a history of chronic anemia (80-100 g/L), previous low white blood cell levels (3-4×109/L), or reduced platelets (80-90×109/L). Liver function: ALT and AST \<1.5 times the upper limit of normal (ULN), bilirubin \<1.5×ULN. Renal function: Serum creatinine (SCR) ≤140 μmol/L.
* Patients are required to provide informed consent to undergo treatment.

Exclusion Criteria:

* Existing or prior history of other malignant tumors (except non-melanoma skin cancer) that are uncontrolled or not cured, depending on the type of the primary tumor.
* Lack of histological or cytological diagnosis for esophageal cancer.
* Previous chest radiotherapy.
* Suffering from innate or acquired immune function defects;
* Pregnancy (confirmed by serum or urine β-HCG test) or during the lactation period; History of drug abuse or alcohol dependence; HIV-positive status, including those on antiretroviral treatment; Chronic hepatitis B with viral replication phase; Active phase of hepatitis C; Active syphilis with a history of mental illness that may hinder treatment completion.
* Poor overall health status, defined as KPS \< 70 or ECOG \> 2.
* Presence of severe comorbidities that could impact radiotherapy progress, including: Unstable angina, congestive heart failure, or myocardial infarction requiring hospitalization within the past 6 months; Acute bacterial or systemic fungal infections; Exacerbation of chronic obstructive pulmonary disease or other respiratory conditions requiring hospitalization; Hepatic or renal insufficiency; Immunosuppressed patients; Coexisting connective tissue diseases, such as active scleroderma or lupus, which are contraindications to radiotherapy.
* Inability to comprehend the treatment's purpose or unwillingness to sign the treatment consent form.
* Lack of legal capacity or limited legal capacity.

Primary outcomes:
measure: 1-year progression-free survival
timeFrame: 1 year
Secondary outcomes:
measure: Acute toxicity
timeFrame: 3 months
measure: Quality of Life (QoL)
timeFrame: 1 years
measure: Objective response rate
timeFrame: 1 year
measure: Duration of response
timeFrame: 1 year
measure: Disease control rate
timeFrame: 1 year
measure: Immune Progression Free Survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin hospital, Shanghai jiaotong university school of medicine
state: Shanghai
Study officials:
References: