Combining immunotherapy with targeted radiotherapy and chemotherapy for advanced esophageal cancer

Tumor Draining Lymph Nodes Sparing Radiotherapy Plus Immunotherapy and Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: a Randomized Phase III Trial

This study is testing if adding immunotherapy to a combination of targeted radiotherapy and chemotherapy can help people with advanced esophageal cancer feel better and improve their treatment results.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 432 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06676449 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of immunotherapy combined with tumor draining lymph nodes-sparing radiotherapy (TDLN-sparing RT) and chemotherapy in treating locally advanced esophageal squamous cell carcinoma (ESCC). Participants will receive TDLN-sparing RT along with chemotherapy (Paclitaxel and Cisplatin) and either PD-1 inhibitors or observation over a year. The study compares the outcomes of the immunotherapy group against those receiving only TDLN-sparing RT and chemotherapy. The goal is to determine if the addition of immunotherapy enhances treatment efficacy for this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed locally advanced esophageal squamous cell carcinoma.

Not a fit: Patients with esophageal perforation, active autoimmune diseases, or those with certain organ function impairments may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with locally advanced esophageal squamous cell carcinoma.

How similar studies have performed: Other studies have shown promise in using immunotherapy in combination with chemotherapy for various cancers, suggesting potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent
2. Aged 18-75 years
3. Histologically confirmed esophageal squamous cell carcinoma
4. Clinical stages T2-4N0M0 or TxN+M0 or TxNxM1 (Only for supraclavicular lymph nodes metastasis) based on the 8th UICC-TNM classification

7\. Eastern Cooperative Oncology Group(ECOG) performance status: 0-1 8. Life expectancy ≥3 months 9. Adequate organ functions Absolute neutrophil counts (ANC) ≥1.5×109⁄L; Hemoglobin (Hb) ≥9g⁄dl; Platelet (Plt) ≥100×109⁄L; Total bilirubin ≤1.5 upper limit of normal (ULN); Aspartate transaminase (AST) ≤2.5 ULN; Alanine aminotransferase (ALT) ≤2.5 ULN; Creatinine ≤1.5 ULN 10.Received no more than 3 cycles immunotherapy and/or chemotherapy

Exclusion Criteria:

1. Esophageal perforation or hematemesis
2. Any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism and hypothyroidism (effective hormone replacement therapy excepted)) and immunosuppressive agents or systemic hormonal therapy indicated within 28 days (for adverse events of chemoradiotherapy excepted).
3. Allergic to macromolecular protein preparations, or to any of the ingredients in PD-1 inhibitors for injection.
4. Uncontrolled heart diseases or clinical symptoms, such as: (1) New York Heart Association(NYHA) class II or higher heart failure; (2) unstable angina; (3) myocardial infarction within 1 year; (4)clinically significant arrhythmia requiring clinical intervention.
5. Congenital or acquired immunodeficiency (such as HIV infection); active hepatitis B (HBV-DNA≥104 copy number/ml) or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the detection limit of the analytical method); active tuberculosis.
6. Active infection or unexplained fever \>38.5 °C within 2 weeks before randomization (fever due to tumor excepted, according to investigator).
7. Patients with fertility reluctant to take contraceptive measures during the trial, or female patients pregnant or breastfeeding.
8. According to the investigator, other factors that may cause termination of the study. ie, other serious diseases (including mental illness) require combined treatment, family or social factors, which may affect the safety or the collection of trial data.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Dashan Zhao

Conditions Esophageal Carcinoma; Radiotherapy; Immunotherapy