Exploratory Clinical Trial of Oral Paclitaxel Plus Radiotherapy in Patients With Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

Exploratory Clinical Trial of Oral Paclitaxel Plus Radiotherapy in Patients With Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

This study aims to investigate the safety and efficacy of oral paclitaxel combined with radiotherapy in the treatment of locally advanced unresectable esophageal squamous cell carcinoma.

There remains a considerable unmet medical need for first-line treatment in patients with locally advanced, unresectable esophageal squamous cell carcinoma who are intolerant to concurrent intravenous chemotherapy and present with severe obstruction. Therefore, this prospective, single-arm, single-center exploratory study aims to evaluate the safety and efficacy of oral paclitaxel combined with radiotherapy in the treatment of locally advanced, unresectable esophageal squamous cell carcinoma, and to investigate the survival benefit provided for this patient population.

Inclusion Criteria:

1. Histologically confirmed locally advanced unresectable esophageal squamous cell carcinoma (cTXN+M0 or cT2-T4aNXM0).
2. Considered eligible for definitive chemoradiotherapy.
3. Age ≥ 70 years and/or intolerant to intravenous chemotherapy due to comorbidities, with severe dysphagia/feeding obstruction.
4. Disease evaluable by qualitative radiologic assessment per the local investigator.
5. Not eligible for curative surgery.
6. Adequate hematologic function, defined as: ANC ≥ 1500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L.
7. Adequate renal function, defined as: creatinine ≤ 1.5 × ULN; or for patients with creatinine > 1.5 × ULN, measured or calculated creatinine clearance ≥ 60 mL/min.
8. Adequate hepatic function, defined as: total bilirubin ≤ 1.5 × ULN; or for patients with total bilirubin > 1.5 × ULN, direct bilirubin ≤ ULN provided ALT/AST ≤ 2.5 × ULN and albumin ≥ 3.0 g/dL.
9. Adequate coagulation function, defined as: INR ≤ 1.5 × ULN, unless the patient is on anticoagulant therapy with PT or aPTT within the therapeutic range.
10. Negative urine or serum pregnancy test within 24 hours prior to the first dose of study intervention.
11. Voluntary participation in the study, signed written informed consent, good compliance, and willingness to comply with follow-up procedures.

Exclusion Criteria:

1. Direct tumor invasion into adjacent organs, such as the aorta or trachea (i.e., T4b disease).
2. Prior chemotherapy or radiotherapy for esophageal cancer.
3. Any prior systemic anticancer therapy for esophageal cancer.
4. Major surgery other than feeding tube insertion, open biopsy, or significant trauma within 28 days before randomization, or anticipated major surgery during study treatment.
5. History of other malignancy within the past 5 years, except carcinoma in situ of the cervix or basal cell carcinoma.
6. Gastric fistula or esophageal fistula.
7. Active infection requiring systemic therapy.
8. Known history of HIV, HBV, or HCV infection.
9. Participation in a study of an investigational drug or device within 4 weeks prior to the first study treatment.
10. History of non-infectious pneumonitis requiring corticosteroid therapy, or current pneumonitis.
11. Known hypersensitivity to any study drug.
12. Inability or unwillingness to comply with protocol requirements as assessed by the investigator.