Chemoradiotherapy Plus Anti-PD1 in Recurrent NPC: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Официальное название

Chemoradiotherapy Combined With Programmed Death 1 Antibody in Recurrent Nasopharyngeal Carcinoma: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Обзор

This is a multicenter, open-label, randomized, controlled, phase III trial. The purpose of this trial is to evaluate the efficacy and toxicity of anti-PD-1 antibody combined with chemoradiotherapy versus chemoradiotherapy alone in recurrent nasopharyngeal carcinoma patients.

Вмешательства

• Препарат Toripalimab
  240mg, D1, every 3 weeks per cycle, three cycles with chemotherapy and eight cycles after IMRT
• Препарат Chemotherapy
  Gemcitabine: 1.0g/m2, D1 and D8, Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles
• Лучевая терапия Intensity modulated radiotherapy
  total 60-66Gy, 1.8-2.0Gy/f/day

Первичные конечные точки

• Overall survival [Срок оценки: three years]

Вторичные конечные точки (7)

• Failure-free survival [Срок оценки: three years]
• Objective response rate through study completion, an average of nine months [Срок оценки: through study completion, an average of nine months]
• Disease control rate through study completion, an average of nine months [Срок оценки: through study completion, an average of nine months]
• Incidence of nasopharyngeal necrosis and hemorrhage up to 3 years [Срок оценки: up to three-year follow-up]
• Acute toxicities were graded using the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0) [Срок оценки: through study completion, an average of nine months]
• Late toxicity [Срок оценки: three years]
• Quality of life through study completion, up to 3 years [Срок оценки: up to three-year follow-up]

Критерии участия

Критерии включения

• Diagnosed as local with or without regional recurrence after ≥1 year of radical treatment;
• Not suitable for surgery;
• Histologic diagnosis of NPC (WHO II/III);
• TNM stage rII-IVa (AJCC/UICC 8th);
• ECOG 0-1 point;
• No treatment to rNPC prior, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
• No contraindications to immunotherapy or chemoradiotherapy;
• Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
• Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
• Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
• Take effective contraceptions during and two months after treatment;
• Patients must be informed of the investigational nature of this study and give written informed consent.

Критерии исключения

• Treated with anti-tumor Chinese medicine treatment;
• Have recurrence with local necrosis;
• Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
• Unexplained fever > 38.5, except for tumor fever;
• Treated with ≥ 5 days antibiotics one month before enrollment;
• Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy); Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive; Have previously treated with PD-1 antibody or other immunotherapy for PD-1/PD-L1 pathway;
• Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
• Have known allergy to large molecule protein products or any compound of study therapy;
• Pregnant or breastfeeding;
• Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
• Have received a live vaccine within 30 days of planned start of study therapy Has psychiatric drug or substance abuse disorders that would interfere with cooperation with the requirements of the trial;
• Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

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 · 12 центров

• Sun Yat-sen University Cancer Center — Гуанчжоу
• Peking University Third Hospital — Пекин
• Sichuan Cancer Hospital — Чэнду
• Fujian Province Cancer Hospital — Фучжоу
• Guizhou Cancer Hospital — Guiyang
• Zhejiang Cancer Hospital — Ханчжоу
• Jiangxi Cancer Hospital — Nanchang
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• … и ещё 4 центра

Идентификаторы

NCT: NCT05340491 · B2022-111-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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