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

Fudan University

Status and phase: Enrolling; Phase 3

Conditions: Esophageal Carcinoma; Immunotherapy; Radiotherapy

Treatments: Drug: chemotherapy: Paclitaxel/Cisplatin or other guideline recommended regimens; Radiation: TDLN-sparing RT; Drug: Immunotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06676449

ESO-Shanghai 26

Details and patient eligibility

About

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

Enrollment: 432 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

432 participants in 2 patient groups

Concurrent Immunotherapy plus TDLN-sparing RT and Chemotherapy

Experimental group

Description:

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, or other guideline recommended regimens for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx.

Treatment:

Drug: Immunotherapy

Radiation: TDLN-sparing RT

Drug: chemotherapy: Paclitaxel/Cisplatin or other guideline recommended regimens

TDLN-sparing RT and Chemotherapy

Active Comparator group

Description:

Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles, or other guideline recommended regimens for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx. It is allowed to accept immunotherapy followed by radiotherapy.

Treatment:

Radiation: TDLN-sparing RT

Drug: chemotherapy: Paclitaxel/Cisplatin or other guideline recommended regimens