Under Whole-course of Immunotherapy, Gradient Fractionated RT with CCT Versus CFRT with CCT for LANPC Who Achieved PR Post Induction Chemotherapy.

Официальное название

Under Whole-course of Immunotherapy, Gradient Fractionated Radiotherapy with Concurrent Chemotherapy Versus Standard Fractionated Radiotherapy with Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma Who Achieved Partial Response After Induction Chemotherapy: a Randomized, Open-label, Multicenter, Phase III Trial.

Обзор

This prospective trial aims to enroll patients with stage III-IVA (AJCC 8th,) locoregionally advanced nasopharyngeal carcinoma (LANPC). Under the condition of full course of PD-1/PD-L1 blockades, patients who achieved radiological partial response after 3 cycles of platinum-based chemotherapy plus PD-1/PD-L1 blockades will be randomized in a 1:1 ratio to receive gradient radiotherapy (reducing the irradiation dose of PET-CT areas without metabolic abnormalities, while maintaining adequate irradiation dose of areas with metabolic abnormalities) or standard dose radiotherapy with concurrent chemotherapy. It is expected to provide a new therapeutic option for locally advanced nasopharyngeal carcinoma at moderate risk.

Вмешательства

• Препарат Full course of PD-1/PD-L1 blockades
  a) Camrelizumab 200mg, b) Toripalimab 240mg, or c) Adebrelimab 1200mg will be started on day 1 of induction chemotherapy and given every 3 weeks for up to 12 cycles, or until intolerable toxicity, or disease progression or withdrawal from the treatment.
• Препарат Cisplatin-based induction chemotherapy
  Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before radiotherapy.
• Лучевая терапия Standard-dose IMRT
  GTVnx/nd:69.96Gy/33Fr/2.12Gy CTV1: 60.60Gy/33Fr/1.82y CTV2: 54.12Gy/33Fr/1.64Gy
• Лучевая терапия Gradient Fractionated IMRT
  GTVresidue: 68Gy/30Fr/2.27Gy GTVmcr: 60Gy/30F/2Gy CTV1:54Gy/30F/1.8Gy CTV2: 48GY/30F/1.60Gy
• Препарат Concurrent Chemotherapy
  Cisplatin 100mg/m2 every 3 weeks for 2 cycles

Первичные конечные точки

• Progress-Free Survival (PFS) [Срок оценки: 3 years]

Вторичные конечные точки (7)

• Overall Survival (OS) [Срок оценки: 3 years]
• Locoregional Relapse-Free Survival (LRRFS) [Срок оценки: 3 years]
• Distant Metastasis-Free Survival (DMFS) [Срок оценки: 3 years]
• The proportion of patients with treatment related acute complications [Срок оценки: 1 year]
• The proportion of patients with treatment related late complications [Срок оценки: 3 years]
• Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) [Срок оценки: 3 years]
• Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
• Tumor staged as III-IVA (AJCC 8th).
• Patients who achieved partial response according to the RECIST criteria on the basis of MRI, PET-CT and endoscopic biopsy after 3 cycles of induction therapy of platinum-based chemotherapy plus immunotherapy.
• Eastern Cooperative Oncology Group performance status ≤1.
• Age: 18-65 years old.
• Adequate organ function:

Adequate marrow function: neutrocyte count≥4×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.

Adequate liver and kidney function: Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 2.5×ULN.; creatinine clearance rate ≥ 60 ml/min or creatinine of no more than 1.5 times the upper normal limit.

• Patients must be informed of the investigational nature of this study and give written informed consent.

Критерии исключения

• Patients who are evaluated as CR or SD or PD after 3 cycles of induction therapy of platinum-based chemotherapy plus PD-1/PD-L1 blockades.
• The laboratory examination value does not meet the relevant standards within 7 days before enrollment.
• The images of PET-CT and enhanced MRI/CT before induction chemotherapy showed necrotic foci in the center of primary tumors or regional lymph nodes.
• The metabolic changes shown by PET-CT images after induction chemotherapy were inconsistent with the changes in the extent of tumor invasion shown by anatomical images such as enhanced MRI/CT.
• The primary and/or cervical metastases of patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (except diagnostic treatment).
• Has a known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
• Has a known or suspected history of autoimmune diseases, including dementia and seizures.
• Patients with recurrence, distant metastasis and other malignant tumors.
• Severe heart disease, lung dysfunction, heart function, lung function below grade 3 (including grade 3)
• Patients who underwent anti-PD-1 /PD-L1 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway) and anti-angiogenic drugs.
• Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
• HIV positive; HBsAg positive and HBV DNA copy number positive (quantitative detection ≥ 1000 cps/ml); chronic hepatitis C with blood screening positive (HCV antibody positive).
• Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
• Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB treatment is ongoing or within 1 year prior to screening.
• Has received a live vaccine; or a systematic glucocorticoid therapy ; or any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) ; any Chinese anti-tumor herbs within 4 weeks prior to enrollment.
• Pregnancy or breastfeeding.
• Other patients who were considered unsuitable by the treating physicians.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Fifth Affiliated Hospital of Sun Yat-sen University — Zhuhai

Идентификаторы

NCT: NCT06675214 · ZDWY.BYAFZZX.074

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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