De-escalated Radiotherapy for Primary Tumor After Neoadjuvant Therapy With Toripalimab Plus Chemotherapy for Nasopharyngeal Carcinoma

Обзор

In the IMRT era, patients with stage II-III (AJCC8th) nasopharyngeal carcinoma achieve high local control. However, survivors are increasingly experiencing late radiation-induced toxicities. A previous study found that reducing the radiation dose to the primary site to 60Gy for patients who achieved partial or complete response to induction chemotherapy resulted in a lower rate of late toxicities and an inferior local control rate. The investigators aim to reduce the radiation dose to the primary site for patients after immunochemotherapy, given the potential of neoadjuvant chemotherapy and immunotherapy to increase response rates and long-term survival. The protocol includes participants with stage II-III (AJCC8th), except T2N0M0, to receive three courses of neoadjuvant gemcitabine plus cisplatin and Toripalimab. If the primary tumour regresses by over 75%, de-escalated radiotherapy with 60Gy will be administered, and participants will receive two cycles of cisplatin and three cycles of Toripalimab during the radiotherapy course. Otherwise, participants will receive conventional radiotherapy and concurrent chemotherapy with cisplatin for two cycles as usual. The aim of this study is to investigate the 3-year local control rate and toxicities of de-escalated radiotherapy.

Вмешательства

• Лучевая терапия de-escalated radiotherapy
  Enrolled patients receive three courses of induction therapy with gemcitabine and cisplatin, along with Toripalimab. After induction therapy, patients with a tumor volume regression of 75% or more and no detectable EBV DNA will receive de-escalated radiotherapy for the primary tumor with 60 Gy. During radiotherapy, patients will receive Cisplatin 100 mg/m2 every three weeks for two courses and Toripalimab 240 mg every three weeks for three courses. If patients do not achieve complete remission a
• Лучевая терапия conventional radiotherapy
  Enrolled patients receive three courses of induction therapy with gemcitabine and cisplatin, along with Toripalimab. After induction therapy, patients with tumor volume regression less than 75% or EBV DNA copy number higher than 0 receive conventional radiotherapy for the primary tumor with 70 Gy. Patients will receive Cisplatin 100 mg/m2, every three weeks for two courses during radiotherapy.

Первичные конечные точки

• local recurrence rate(LRR) [Срок оценки: 3 years]

Вторичные конечные точки (4)

• primary tumor volume regression≥75% rate [Срок оценки: Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days), prior to radiotherapy]
• 3-year overall survival [Срок оценки: 3 years]
• acute and late radiation-induced toxicities [Срок оценки: up to 3 years after radiotherapy, respectively]
• complete response rate of primary tumor [Срок оценки: Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days) and six months after radiotherapy.]

Критерии участия

Критерии включения

• Pathologically confirmed nasopharyngeal carcinoma, patients who have not received anti-cancer therapy;
• ECOG performance status score (PS score) 0 or 1.
• 18-70 years old.
• Stage II-III except T2N0M0 (AJCC 8th).
• Neutrophil count ≥ 1.5 × 10\^9/L, hemoglobin ≥ 90 g/L and platelet count ≥ 100 × 10\^9/L.
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN; Creatinine clearance ≥ 60 ml/min
• Patients are required to sign an informed consent form and must be willing and able to comply with the visits, treatment plan, laboratory tests, and other requirements specified in the study protocol

Критерии исключения

Patients will be excluded from the study, if any of the following criteria is met:

• Over the age of 70 or under the age of 18.
• HBsAg positive and HBV DNA ≥ 1 × 10\^3 copies/ml
• HCV antibody positive.
• Subjects with active, known or suspected autoimmune diseases were excluded from the study. Eligible participants included those with type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not require systemic therapy such as vitiligo, psoriasis, or alopecia.
• History of interstitial lung disease;
• Receiving systemic sex hormones or other immunosuppressive therapy at equivalent doses ≥ 10 mg prednisone/day within 28 days prior to signing informed consent; Subjects with systemic sex hormone doses ≤ 10 mg prednisone/day or inhaled/topical corticosteroids were eligible.
• Received or about to receive live vaccines within 30 days before signing the informed consent form;
• Pregnant or lactating women;
• Other malignancies within 5 years, except carcinoma in situ, adequately treated non-melanoma skin cancer and papillary thyroid cancer;
• Known previous hypersensitivity to macromolecular protein preparations, or to any component of Toripalimab;
• Human immunodeficiency virus (HIV) infection.
• Other conditions that may affect the safety of subjects or trial compliance as judged by the investigator, including symptomatic heart failure, unstable angina pectoris, myocardial infarction, active infection requiring systemic treatment, mental illness or family and social factors;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-Sen University Cancer Center — Гуанчжоу

Публикации

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Идентификаторы

NCT: NCT06313450 · B2023-110-X02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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