Clinical trial NCT06303583: Neoadjuvant Chemoradiotherapy Followed by Sequential Immunotherapy for Thoracic Esophageal Squamous Cell Carcinoma
Official title: Neoadjuvant Chemoradiotherapy Followed by Sequential Immunotherapy for Thoracic Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Neoadjuvant
chemoradiotherapy
tislelizumab
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of study is to investigate the safety and efficacy of sequential immunotherapy with neoadjuvant chemoradiotherapy for esophageal cancer

Detailed description: This is a single-arm, phase Ib study. Eligibility criteria include histologically confirmed ESCC and clinical T3-4aN0M0 or T2-4aN+M0 (AJCC/UICC 8). Patients received neoadjuvant radiotherapy (41.4Gy in 23 fractions) with concurrent chemotherapy (paclitaxel, 50 mg/m2, carboplatin area under the curve of 2mg/mL/min, QW\*5). Then followed by two cycles of tislelizumab (200mg, Q3W). The primary endpoint was the pathological complete response (pCR) rate and safety.

Eligibility criteria: Inclusion Criteria:

* Ages 18-75.
* Histology confirmed thoracic esophageal squamous cell carcinoma.
* ECOG ps 0 to 1.
* Resectable or potentially resectable T2-4aN0 or T1-4aN+ patients (AJCC/UICC Clinical Staging of Esophageal squamous cell Carcinoma, 8th edition (cTMN)).
* Length of esophageal lesions \<8cm.
* There were no surgical contraindications.
* Neutrophil count ≥1.5\*109/L, platelet count ≥10.0\*109/L, hemochrome ≥9g/dL; Serum creatinine ≤1.5 times the upper limit of normal value; Bilirubin ≤1.5 times the upper limit of normal value, AST, ALT, AKP≤2.5 times the upper limit of normal value.
* BMI acuity 18.5 kg/m2.
* Informed notification and signed informed consent.

Exclusion Criteria:

* Cervical esophageal cancer (upper part of the lesion in the cervical esophagus). Multifocal esophageal carcinoma, lesion length \>8cm.
* Trachea and aorta were invaded (Annex 5).
* Hoarseness caused by the tumor.
* Esophageal fistula.
* Lymph node metastasis in the neck and periceliac artery (AJCC/UICC 8th edition esophageal/esophagogastric junction region lymph node division 1 and 20).
* A history of active autoimmune disorders or syndromes requiring treatment with systemic steroids or immunosuppressants (except for vitiligo or cured childhood asthma/allergies who do not require any intervention in adulthood; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone).
* She is on hormonal or immunosuppressive therapy.
* He's had an organ transplant.
* HIV infection, hepatitis C (hepatitis C antibody positive with HCV-RNA above the detection limit of the assay), chronic active hepatitis B (HBV DNA≥2×103IU/ml or \>1×104copies/mL).
* Active tuberculosis, interstitial pneumonia, active infection, poorly controlled diabetes, symptomatic arrhythmia, symptomatic new dysfunction, myocardial infarction, active peptic ulcer, chronic active enteritis within 6 months; Affected during pregnancy or lactation.
* Major surgery in the last three months.
* Severe diabetes mellitus with poor drug control, symptomatic arrhythmia, symptomatic cardiac insufficiency, myocardial infarction within 6 months, chronic active enteritis, chronic nephritis. QTc acuity 470 ms.
* He had a history of malignancy. Previously received chemotherapy, radiotherapy, targeted therapy, immunotherapy and other antitumor therapies.
* Patients with allergic or contraindicated taxa.
* Live vaccine is administered within 30 days before the first dose of immunotherapy.
* Refusal or inability to sign up for ICF study.
* The investigator decided that the patient was not suitable to participate.

Primary outcomes:
measure: Complete pathological response rate
timeFrame: 1 year
Secondary outcomes:
measure: R0 resection rate
timeFrame: 1 year
measure: 2-year Disease-free survival rate
timeFrame: 2 years
measure: 2-year overall survival rate
timeFrame: 2 years
measure: Safety will be analyzed through the incidence of adverse events, serious adverse events
timeFrame: Up to 28 days from last dose
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: