Individualized Primary Clinical Target Volume Based on Margin Expansion for Nasopharyngeal Carcinoma

Официальное название

Individualized Primary Clinical Target Volume Based on Margin Expansion for Nasopharyngeal Carcinoma: A Non-Inferiority, Multicenter, Randomized Phase 3 Trial

Обзор

This is a non-inferiority, multicenter, randomized phase 3 trial aimed at investigating the impact of individualized primary clinical target volume based on margin expansion on patients' prognosis and complications compared with the consensus primary clinical target volume based on margin expansion and stepwise extension pattern for patients with newly diagnosed non-metastatic nasopharyngeal carcinoma.

Подробное описание

The goals of this clinical trial are: a) To confirm whether the local failure-free survival of patients with nasopharyngeal carcinoma whose primary clinical target volume is delineated based on margin expansion is non-inferior to the local failure-free survival of patients whose primary clinical target volume is delineated according to the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas; b) To explore the impact of the individualized primary clinical target volume based on margin expansion on the overall survival, failure-free survival, distant failure-free survival, locoregional failure-free survival, and regional failure-free survival of patients with nasopharyngeal carcinoma; c) To explore the impact of the individualized primary clinical target volume based on margin expansion on radiotherapy-related complications and quality of life; d) To explore the impact of the individualized primary clinical target volume based on margin expansion on the tumor immune microenvironment, along with its underlying biological mechanisms.

For these purposes, we plan to prospectively enroll patients with newly diagnosed non-metastatic nasopharyngeal carcinoma from hospitals in China. The participants will be randomized into the experimental group and the control group. Comprehensive therapy for participants in both groups will be designed based on tumor stage according to the current clinical guidelines for the management of nasopharyngeal carcinoma. During the radiotherapy, the primary clinical target volume will be delineated based on margin expansion for the experimental group, while the primary clinical target volume will be delineated based on margin expansion and local stepwise extension patterns according to the CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas for the control group. The prognosis, complications, and quality of life will be compared between the experimental group and the control group.

Вмешательства

• Процедура Comprehensive Therapy Based on Tumor Stage
  1. T1N0: Radiotherapy Only. 2. T1N1, T2N0-1, T3N0: Radiotherapy with or without Concurrent Chemotherapy (Cisplatin). 3. T3N1, T4N0: Concurrent Chemoradiotherapy (Cisplatin) with or without Induction Chemotherapy (GP Regimen). 4. T1-4N2-3, T4N1: ① Induction Chemotherapy (GP Regimen) + Concurrent Chemoradiotherapy (Cisplatin); ② Induction Chemoimmunotherapy (GP Regimen + PD-1 Monoclonal Antibody) + Concurrent Chemoradiotherapy (Cisplatin) + Adjuvant Immunotherapy (PD-1 Monoclonal Antibody).
• Лучевая терапия IMRT with Individualized Primary Clinical Target Volume Based on Margin Expansion
  1. Target delineation: 1. CTVp\_High = GTVp + 0 mm 2. CTVp\_Mid = CTVp\_High + 5 mm 3. CTVp\_Low = CTVp\_Mid + 5 mm + whole nasopharynx 4. CTVn\_High = GTVn + 0 mm 5. CTVn\_Mid = CTVn\_High + 3-5 mm (for nodes with imaging-detected extranodal extension) or 0 mm (for nodes without imaging-detected extranodal extension) + equivocal nodes in the anticipated drainage levels, close proximity to enlarged nodes, or with suspicious PET results 6. CTVn\_Low = CTVn\_Mid + 3 mm + electiv
• Лучевая терапия IMRT with Consensus Primary Clinical Target Volume
  1. Target delineation: 1. CTVp\_High = GTVp + 0 mm 2. CTVp\_Mid = CTVp\_High + 5 mm 3. CTVp\_Low = CTVp\_Mid + 5 mm + whole nasopharynx + high-risk structures based on stepwise local extension patterns of tumor spread 4. CTVn\_High = GTVn + 0 mm 5. CTVn\_Mid = CTVn\_High + 3-5 mm (for nodes with imaging-detected extranodal extension) or 0 mm (for nodes without imaging-detected extranodal extension) + equivocal nodes in the anticipated drainage levels, close proximity to enlarged

Первичные конечные точки

• Local failure-free survival (LFFS) [Срок оценки: 3 years]

Вторичные конечные точки (8)

• Overall survival (OS) [Срок оценки: 3 years]
• Failure-free survival (FFS) [Срок оценки: 3 years]
• Distant failure-free survival (DFFS) [Срок оценки: 3 years]
• Locoregional failure-free survival (LRFFS) [Срок оценки: 3 years]
• Regional failure-free survival (RFFS) [Срок оценки: 3 years]
• Incidence rate of investigator-reported radiotherapy-related complications [Срок оценки: Within (acute complication) / since (late complication) 90 days after the radiotherapy onset.]
• Incidence rate of patient-reported adverse events [Срок оценки: Periprocedural.]
• Quality of life (QoL): questionnaire [Срок оценки: Up to 5 years.]

Критерии участия

Критерии включения

• Age: 18 Years to 65 Years.
• Eastern Cooperative Oncology Group performance status ≤1.
• Patients with newly diagnosed, histologically confirmed nasopharyngeal carcinoma (non-keratinizing subtype).
• Tumor staged as T1-4N0-3M0 (AJCC 9th).
• Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule.
• Women of childbearing potential and male subjects with female partners of childbearing potential must agree to use reliable contraceptive measures from screening to 1 year after treatment.
• For subjects requiring chemotherapy, the following are additionally required:

• normal bone marrow function (white blood cell count > 4 × 10\^9/L, hemoglobin > 90 g/L, platelet count > 100 × 10\^9/L);
• normal liver and kidney function (total bilirubin ≤ 1.5 × upper limit of normal, alanine transaminase and aspartate transaminase ≤ 2.5 × upper limit of normal, alkaline phosphatase ≤ 2.5 × upper limit of normal, creatinine clearance rate ≥ 60 mL/min).

Критерии исключения

• Active tuberculosis: active tuberculosis within the past 1 year should be excluded regardless of treatment; a history of active tuberculosis > 1 year ago is exclusionary unless prior adequate anti-tuberculosis treatment is documented.
• Active infection requiring systemic treatment.
• Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer.
• History of radiotherapy, except for non-melanoma skin cancer located outside the target volume of radiotherapy for nasophayngeal carcinoma.
• Prior or concurrent treatment for local or regional disease other than that specified in the research plan.
• Pregnant or lactating women (a pregnancy test is required for women of childbearing potential).
• Contraindications to MRI examination, for example: claustrophobia, allergy to MRI contrast.
• History of psychiatric disorders, alcoholism or drug abuse, and other situations assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors.
• For participants requiring chemotherapy, the following must also be excluded:

• anti-human immunodeficiency virus positive or diagnosed with acquired immune deficiency syndrome;
• uncontrolled heart disease (heart failure \[NYHA Class ≥ 2\], unstable angina, myocardial infarction in past 1 year, supraventricular or ventricular arrhythmia requiring treatment or intervention).
• For participants requiring immunotherapy, the following must also be excluded:

• hepatitis B virus surface antigen positive and Hepatitis B virus DNA > 1000 copies/mL;
• anti-hepatitis C virus positive;
• active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary disease, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchodilators, exceptions are type I diabetes mellitus, hypothyroidism not requiring hormone replacement therapy, skin disorders not requiring systemic treatment \[such as vitiligo, psoriasis or alopecia\]);
• previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
• chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day, subjects who use inhaled or topical corticosteroids are eligible) or any other form of immunosuppressive therapy;
• allergy to macromolecular protein preparations, or any component of PD-1 monoclonal antibody;
• receiving live vaccine within 30 days prior to the first dose of PD-1 monoclonal antibody.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Dongguan People's Hospital — Дунгуань
• Sun Yat-Sen University Cancer Center — Гуанчжоу
• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen — Шэньчжэнь
• Hunan Cancer Hospital — Чанша
• Xiangya Hospital Central South University — Чанша

Публикации

• Wong KCW, Hui EP, Lo KW, Lam WKJ, Johnson D, Li L, Tao Q, Chan KCA, To KF, King AD, Ma BBY, Chan ATC. Nasopharyngeal carcinoma: an evolving paradigm. Nat Rev Clin Oncol. 2021 Nov;18(11):679-695. doi: 10.1038/s41571-021-00524-x. Epub 2021 Jun 30. PMID 34194007
• Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019 Jul 6;394(10192):64-80. doi: 10.1016/S0140-6736(19)30956-0. Epub 2019 Jun 6. PMID 31178151
• Liang YL, Liu X, Shen LF, Hu GY, Zou GR, Zhang N, Chen CB, Chen XZ, Zhu XD, Yuan YW, Yang KY, Jin F, Hu WH, Xie FY, Huang Y, Han F, Tang LL, Mao YP, Lu LX, Sun R, He YX, Zhou YY, Long GX, Tang J, Chen LS, Zong JF, Jin T, Li L, Lin J, Huang J, Gong XY, Zhou GQ, Chen L, Li WF, Chen YP, Xu C, Lin L, Huang SH, Huang SW, Wang YQ, Huang CL, Feng HX, Hou M, Chen CH, Zheng SF, Li YQ, Hong SB, Jie YS, Li H PMID 40079940
• Liu X, Zhang Y, Yang KY, Zhang N, Jin F, Zou GR, Zhu XD, Xie FY, Liang XY, Li WF, He ZY, Chen NY, Hu WH, Wu HJ, Shi M, Zhou GQ, Mao YP, Guo R, Sun R, Huang J, Liang SQ, Wu WL, Su Z, Li L, Ai P, He YX, Zang J, Chen L, Lin L, Huang SH, Xu C, Lv JW, Li YQ, Hong SB, Jie YS, Li H, Huang SW, Liang YL, Wang YQ, Peng YL, Zhu JH, Zang SB, Liu SR, Lin QG, Li HJ, Tian L, Liu LZ, Zhao HY, Lin AH, Li JB, Liu N PMID 38824941
• Lee N, Xia P, Quivey JM, Sultanem K, Poon I, Akazawa C, Akazawa P, Weinberg V, Fu KK. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):12-22. doi: 10.1016/s0360-3016(02)02724-4. PMID 12007936
• Lee N, Harris J, Garden AS, Straube W, Glisson B, Xia P, Bosch W, Morrison WH, Quivey J, Thorstad W, Jones C, Ang KK. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol. 2009 Aug 1;27(22):3684-90. doi: 10.1200/JCO.2008.19.9109. Epub 2009 Jun 29. PMID 19564532
• Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012 Feb;13(2):172-80. doi: 10.1016/S1470-2045(11)70303-5. Epub 2011 Dec 15. PMID 22178121
• Liang SB, Sun Y, Liu LZ, Chen Y, Chen L, Mao YP, Tang LL, Tian L, Lin AH, Liu MZ, Li L, Ma J. Extension of local disease in nasopharyngeal carcinoma detected by magnetic resonance imaging: improvement of clinical target volume delineation. Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):742-50. doi: 10.1016/j.ijrobp.2008.11.053. Epub 2009 Feb 27. PMID 19251378

Идентификаторы

NCT: NCT07661771 · 2026-FXY-200-FLK

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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