Toripalimab for Local-regional Recurrent Nasopharyngeal Carcinoma

Официальное название

Toripalimab in Combination With Concurrent Chemoradiotherapy for Local-regional Recurrent Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial

Обзор

This is a phase 3, multicentre, randomised controlled trial to study the effectiveness and toxicity of PD-1 antibody Toripalimab combined with concurrent cisplatin chemoradiotherapy versus cisplatin concurrent chemoradiotherapy alone in treating patients with locoregionally recurrent nasopharyngeal carcinoma.

Подробное описание

Nasopharyngeal carcinoma (NPC) is endemic in southern China, southeast Asia, and northern Africa. According to a survey from the International Agency for Research on Cancer, there were an estimated 129,079 new cases and 72,987 related deaths in 2018. Radiotherapy is the primary treatment option. Due to advances in disease management, diagnostic imaging, radiotherapy technology, and the broader application of systemic therapy, the prognosis of NPC has improved signifificantly.Nevertheless, localregional recurrence will occur in about 10% patients. Because of radiation resistance, the prognosis of re-irradiation is poor for recurrent nasopharyngeal carcinoma.

Hence, there is an urgent need for novel therapies to improve survival and reduce treatment-related toxicity in recurrent NPC patients. Emerging evidence shows that PD-1 antibody is effective for treating recurrent/metastastic NPC patients. This is a phase 3, multicentre, randomised controlled trial to study the effectiveness and toxicity of neoadjuvant and adjuvant PD-1 antibody Toripalimab combined with concurrent chemoradiotherapy (CCRT) versus CCRT alone in treating patients with locoregionally recurrent nasopharyngeal carcinoma.

Вмешательства

• Препарат Toripalimab
  anti-PD-1 antibody

Первичные конечные точки

• Overall survival (OS) [Срок оценки: 5 years]

Вторичные конечные точки (4)

• Progress-free survival (PFS) [Срок оценки: 5 years]
• Objective Response Rate (ORR) [Срок оценки: 3 months]
• Incidence rate of adverse events (AEs) [Срок оценки: 5 years]
• Change of QoL (quality of life) [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Patients with newly histologically confirmed recurrent nasopharyngeal carcinoma, or Two or more image examinations (MRI, and PET-CT) show the recurrent tumor
• staged as rT3-4N0-1M0或rT1-4N2-3M0 （according to the 8th AJCC edition）
• Satisfactory performance status: ECOG (Eastern Cooperative OncologyGroup) scale 0-1
• Neutrophil ≥ 1.5×109 /L and PLT ≥4×109 /L and HGB ≥90 g/L
• With normal liver function test (ALT、AST ≤ 2.5×ULN, TBIL≤ 1.5×ULN)
• With normal renal function test ( creatinine clearance ≥60 ml/min)
• sign an "informed consent form
• Male and no pregnant female

Критерии исключения

• Age older than 65, or younger than 18 years old
• Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥200IU/ml, or 1000cps/ml.
• Patients with positive HCV antibody.
• Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy, and skin disease (leukoderma, psoriasis, alopecia et al) who don't need systemic therapy can recruit.
• History of interstitial lung disease
• Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent.
• Receive or will receive live vaccine within 30 days prior to signing the informed consent.
• Women of child-bearing potential who are pregnant or breastfeeding.
• Suffered from malignant tumors, except the carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years.
• Hypersensitivity to macromolecular protein, or to any component of triplezumab.
• HIV positive.
• Severe, uncontrolled medical conditions and infections.
• Other diseases which may influence the safety or compliance of the clinical trial, such as heart failure with symptom, unstable angina, myocardial infarction, active infections those need systemic therapy, mental illness, or their family and society factors.

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

• Guangxi Medical University Cancer Hospital — Nanning

Публикации

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. PMID 30207593
• Chua MLK, Wee JTS, Hui EP, Chan ATC. Nasopharyngeal carcinoma. Lancet. 2016 Mar 5;387(10022):1012-1024. doi: 10.1016/S0140-6736(15)00055-0. Epub 2015 Aug 28. PMID 26321262
• Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. doi: 10.1146/annurev.immunol.26.021607.090331. PMID 18173375
• Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001 Mar;2(3):261-8. doi: 10.1038/85330. PMID 11224527
• Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006 Feb 9;439(7077):682-7. doi: 10.1038/nature04444. Epub 2005 Dec 28. PMID 16382236
• Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, Yu H, Fletcher CD, Freeman GJ, Shipp MA, Rodig SJ. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013 Jul 1;19(13):3462-73. doi: 10.1158/1078-0432.CCR-13-0855. Epub 2013 May 14. PMID 23674495
• Fang W, Zhang J, Hong S, Zhan J, Chen N, Qin T, Tang Y, Zhang Y, Kang S, Zhou T, Wu X, Liang W, Hu Z, Ma Y, Zhao Y, Tian Y, Yang Y, Xue C, Yan Y, Hou X, Huang P, Huang Y, Zhao H, Zhang L. EBV-driven LMP1 and IFN-gamma up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy. Oncotarget. 2014 Dec 15;5(23):12189-202. doi: 10.18632/oncotarget.2608. PMID 25361008
• Dong H, Chen L. B7-H1 pathway and its role in the evasion of tumor immunity. J Mol Med (Berl). 2003 May;81(5):281-7. doi: 10.1007/s00109-003-0430-2. Epub 2003 Apr 30. PMID 12721664

Идентификаторы

NCT: NCT04376866 · CS2020(7)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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