TDLN-sparing RT Plus Immunotherapy and Chemotherapy in Locally Advanced ESCC

Phase 3

Recruiting

• Conditions: Esophageal Carcinoma; Radiotherapy; Immunotherapy
• Interventions: Drug: Immunotherapy; Radiation: TDLN-sparing RT

• Registration Number: NCT06676449
• Lead Sponsor: Fudan University

Brief Summary

The goal of this clinical trial is to learn if immunotherapy in combination with tumor draining lymph nodes-sparing radiotherapy (TDLN-sparing RT) and chemotherapy works to treat locally advanced esophageal squamous cell cancer in adults.

Researchers will compare immunotherapy in combination with TDLN-sparing RT and chemotherapy to TDLN-sparing RT and chemotherapy to see if immunotherapy works more effectively when using TDLN-sparing RT to treat locally advanced esophageal squamous cell cancer

Participants will:

TDLN-sparing RT for esophageal cancer 50.4Gy/28Fx Paclitaxel plus cisplatin every 3 weeks for 4 cycles PD-1 inhibitors or observation every 3 weeks for 1 year

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study Start: 2024-11-01
• Study First Submitted: 2024-11-05
• Study First Submitted QC: 2024-11-05
• Study First Posted: 2024-11-06
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-07
• Primary Completion: 2028-10-31
• Study Completion: 2030-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 432

Inclusion Criteria

1. Written informed consent

2. Aged 18-75 years

3. Histologically confirmed esophageal squamous cell carcinoma

4. Clinical stages T3-4N0M0 or TxN1M0 or TxNxM1a or TxNxM1b (Only for cervical lymph nodes or celiac lymph nodes metastasis) based on the 6th UICC-TNM classification

5. 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

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. Previously received or receiving PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1.
4. Allergic to macromolecular protein preparations, or to any of the ingredients in PD-1 inhibitors for injection.
5. 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.
6. 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.
7. Active infection or unexplained fever >38.5 °C within 2 weeks before randomization (fever due to tumor excepted, according to investigator).
8. Patients with fertility reluctant to take contraceptive measures during the trial, or female patients pregnant or breastfeeding.
9. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immunotherapy plus TDLN-sparing RT and Chemotherapy	Immunotherapy	PD-1 inhibitors will be administered intravenously, a fixed dose of 200 mg, once every 3 weeks for 1 year. Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx.
Immunotherapy plus TDLN-sparing RT and Chemotherapy	TDLN-sparing RT	PD-1 inhibitors will be administered intravenously, a fixed dose of 200 mg, once every 3 weeks for 1 year. Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx.
TDLN-sparing RT and Chemotherapy	TDLN-sparing RT	Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx.

Primary Outcome Measures

Name	Time	Method
PFS for patients with TDLN V15 ≤ 50%	2 years
PFS for all patients	2 years

Secondary Outcome Measures

Name	Time	Method
OS for all patients	2 years
OS for patients with TDLN V15 ≤ 50%	2 years
Adverse events	up to 2 years

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China