Clinical trial NCT06676449: TDLN-sparing RT Plus Immunotherapy and Chemotherapy in Locally Advanced ESCC
Official title: Tumor Draining Lymph Nodes Sparing Radiotherapy Plus Immunotherapy and Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: a Randomized Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Carcinoma
Radiotherapy
Immunotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-11-06
Enrollment: 432
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

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

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.

Primary outcomes:
measure: PFS for patients with TDLN V15 ≤ 50%
timeFrame: 2 years
measure: PFS for all patients
timeFrame: 2 years
Secondary outcomes:
measure: OS for patients with TDLN V15 ≤ 50%
timeFrame: 2 years
measure: OS for all patients
timeFrame: 2 years
measure: Adverse events
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: