TDLN-sparing RT Followed by PD-1 Inhibitor Maintenance Therapy in Locally Advanced ESCC

Fudan University

Status and phase: Enrolling; Phase 3

Conditions: Esophageal Carcinoma; Immunotherapy; Radiotherapy

Treatments: Radiation: TDLN-sparing radiotherapy; Radiation: Unlimited radiotherapy; Drug: PD-1 inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT06964568

ESO-Shanghai 27

Details and patient eligibility

About

The goal of this clinical trial is to learn if tumor draining lymph nodes-sparing radiotherapy (TDLN-sparing RT) followed by immunotherapy as maintenance therapy works to treat locally advanced esophageal squamous cell cancer in adults.

Enrollment: 452 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Written informed consent
2. Aged 18 years or above
3. Histologically confirmed esophageal squamous cell carcinoma
4. Clinical stages T3-4N0M0 or TxN+M0 or TxNxM1 (Only for supraclavicular lymph nodes) 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

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 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).

   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)

---

452 participants in 4 patient groups

TDLN-sparing RT and PD-1 inhibitor maintenance therapy

Experimental group

Description:

TDLN-sparing radiotherapy 50.4Gy/28Fx. PD-1 inhibitors will be administered intravenously, a fixed dose of 200 mg, once every 3 weeks for 1 year followed by radiotherapy.

Treatment:

Drug: PD-1 inhibitor

Radiation: TDLN-sparing radiotherapy

TDLN-sparing RT and surveillance

Experimental group

Description:

TDLN-sparing radiotherapy 50.4Gy/28Fx.

Treatment:

Radiation: TDLN-sparing radiotherapy

Unlimited RT and PD-1 inhibitor maintenance therapy

Experimental group

Description:

Unlimited radiotherapy 50.4Gy/28Fx. PD-1 inhibitors will be administered intravenously, a fixed dose of 200 mg, once every 3 weeks for 1 year followed by radiotherapy.

Treatment:

Drug: PD-1 inhibitor

Unlimited RT and surveillance

Active Comparator group

Description:

Unlimited radiotherapy 50.4Gy/28Fx.

Treatment:

Radiation: Unlimited radiotherapy