RecruitingNot ApplicableNCT06792786

A Multicenter Prospective Study Evaluating Concurrent Chemoradiotherapy Following Induction Immunochemotherapy for Esophageal Cancer Based on Dynamic ctDNA Monitoring

Sponsor

The Central Hospital of Lishui City

Enrollment

30 participants

Start Date

Dec 10, 2024

Study Type

INTERVENTIONAL

Conditions

Esophageal Cancer ctDNA

Summary

Esophageal squamous cell carcinoma (ESCC) continues to exhibit high incidence and mortality rates in China, with the majority of patients diagnosed at middle to advanced stages. Concurrent chemoradiotherapy (CCRT) is the standard treatment for unresectable locally advanced ESCC. The 5-year survival rate for advanced esophageal cancer remains below 20%. Immunotherapy has demonstrated definitive efficacy and a favorable toxicity profile in advanced ESCC, and preliminary results of its combination with radiotherapy have been reported. Induction immunochemotherapy followed by concurrent chemoradiotherapy represents a feasible combined treatment strategy. However, optimal biomarkers to identify patients who would benefit from this approach are still lacking. Circulating tumor DNA (ctDNA) status can accurately guide treatment implementation and predict tumor progression. Studies have shown that ctDNA changes precede imaging evidence of recurrence or metastasis, and ctDNA detection can sensitively predict tumor progression and prognosis. Therefore, it is necessary to dynamically monitor ctDNA changes throughout the course of induction immunochemotherapy followed by radical concurrent chemoradiotherapy in esophageal cancer and explore its correlation with prognosis.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria12

All subjects must sign an informed consent form before initiating any study-related procedures;
All patients must be aged ≥18 years and ≤75 years;
Histologically or cytologically confirmed esophageal cancer (squamous cell carcinoma);
Clinical stage II-IVa, assessed by a surgeon as inoperable, or patient refusal of surgery;
No prior radiotherapy, chemotherapy, immunotherapy, or biotherapy for esophageal cancer;
ECOG performance status of 0-1;
Laboratory test values within the following limits before the first dose of the investigational drug:
Hematology: WBC ≥3.0×10⁹/L; ANC ≥1.5×10⁹/L; PLT ≥70×10⁹/L; HGB ≥9.0 g/dL;
Liver function: AST ≤2.5×ULN; ALT ≤2.5×ULN;
Renal function: Cr ≤1.5×ULN or CrCl ≥40 mL/min;
Coagulation: INR ≤1.5, APTT ≤1.5×ULN;
Other: Lipase ≤1.5×ULN, unless clinically/radiographically insignificant if lipase >1.5×ULN.

Exclusion Criteria9

Insufficient tissue/blood sample available before treatment as required for the study;
Patient refusal to undergo dynamic ctDNA testing;
The primary esophageal lesion is in close proximity to the tracheobronchial tree or major blood vessels, with an investigator-assessed high risk of perforation or major hemorrhage;
History of malignancies other than esophageal carcinoma within the past 5 years (except for curatively treated localized tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or localized prostate cancer);
History of gastrointestinal bleeding within the past 6 months, or coagulopathy at enrollment, or current thrombolytic or anticoagulant therapy indicating a high risk of bleeding;
Severe cardiovascular or cerebrovascular diseases;
History of interstitial lung disease or active pneumonia/tuberculosis;
Severe allergic reactions to paclitaxel/cisplatin or any monoclonal antibody;
Any other condition deemed inappropriate for participation in this study as judged by the investigator.

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Interventions

DIAGNOSTIC_TESTInduction Immunochemotherapy

Induction Immunochemotherapy:Toripalimab 240 mg (immunotherapy) combined with paclitaxel (135 mg/m²) and cisplatin (75 mg/m²) chemotherapy, administered every 3 weeks for 2 cycles. Other Names: - Radiotherapy: 95% PTV 50-50.4 Gy/25-28 fractions, 1.8-2 Gy/fraction; 5 days per week. - Chemotherapy: Weekly paclitaxel (50 mg/m²) combined with cisplatin (25 mg/m²) for 5 cycles. ctDNA Analysis:Initial tissue and blood ctDNA testing prior to treatment (T0) is based on next-generation sequencing (NGS) technology, utilizing tumor-informed assays. Blood ctDNA samples will be collected before chemoradiotherapy, after 20 fractions of radiotherapy, and every 3 months following completion of chemoradiotherapy.