Epirubicin Interventional Chemotherapy for Sinonasal Adenoid Cystic Carcinoma (SNACC): A Prospective Study

Официальное название

A Prospective, Multicenter Study of Transarterial Epirubicin Chemotherapy in the Treatment of Sinonasal Adenoid Cystic Carcinoma

Обзор

This study is for patients with locally advanced sinonasal adenoid cystic carcinoma (SNACC), a rare and challenging cancer that tends to invade nerves and the skull base. The research aims to test a new precise treatment strategy. First, all participants will receive three sessions of "interventional chemotherapy" (transarterial chemoembolization) with the drug Epirubicin, which delivers high-dose chemotherapy directly to the tumor to shrink it as much as possible. About 4-6 weeks after the third session, doctors will use MRI scans to evaluate how well the tumor responded. Based on this response, patients will follow one of two personalized treatment paths: those whose tumors did not completely disappear will undergo surgery followed by radiotherapy; those whose tumors show complete disappearance on imaging will receive precise radiotherapy alone, potentially avoiding major surgery. This is a prospective, multicenter study. The main goals are to evaluate the safety and effectiveness of this response-adapted strategy and to see if it can improve outcomes for patients with this difficult-to-treat cancer.

Подробное описание

1. Background and Rationale Sinonasal adenoid cystic carcinoma (SNACC) is a rare malignancy with a propensity for perineural invasion and skull base infiltration. Complete surgical resection is challenging and often associated with significant morbidity. While systemic chemotherapy offers limited benefit, our preclinical data from patient-derived tumor organoid drug sensitivity testing identified Epirubicin as the most active agent (sensitivity rate: 87.5%, n=24).Transarterial chemoembolization allows for targeted, high-dose drug delivery to the tumor bed while minimizing systemic exposure, presenting a promising neoadjuvant strategy. 2. Study Objectives

Primary Objectives: To evaluate the objective response rate (ORR) after three cycles of transarterial Epirubicin chemoinfusion, the 2-year progression-free survival (PFS) of the integrated strategy, and the safety profile of the interventional chemotherapy.

Secondary Objectives: To assess the complete response (CR) rate post-chemotherapy, the safety of subsequent surgery/radiotherapy, overall survival (OS), and explore biomarkers predictive of response. 3. Study Design This is a prospective, multicenter, single-arm, interventional study. The study employs a response-adapted design. 4. Methodology

Participants: Approximately 100 patients with histologically confirmed, locally advanced (T3/T4) SNACC will be enrolled across multiple centers in China, including \[Fudan University Eye \& ENT Hospital\].

Intervention: All participants will receive three cycles of transarterial Epirubicin chemoinfusion (60mg/m² per cycle, q4w). Central imaging review (MRI, RECIST 1.1) will be performed 4-6 weeks after the third cycle.

Stratified Treatment Pathways:

Path A (Non-CR): Patients not achieving CR will undergo planned skull base surgery followed by adjuvant radiotherapy.

Path B (CR): Patients achieving imaging CR will proceed directly to definitive intensity-modulated radiotherapy (IMRT) without surgery.

Assessments: Efficacy will be assessed via serial contrast-enhanced MRI. Safety will be monitored per CTCAE v5.0, including laboratory tests and cardiac function evaluation (echocardiography).

Statistical Analysis: The sample size is calculated based on demonstrating superiority in ORR compared to a historical benchmark. PFS and OS will be analyzed using the Kaplan-Meier method. Analysis will follow the intention-to-treat principle. 5. Ethics and Dissemination The study protocol has been approved by the Institutional Review Board of \[Fudan University Eye \& ENT Hospital\] (Approval No: \[2025307\]). It will be conducted in accordance with the Declaration of Helsinki. Results will be disseminated through peer-reviewed publications and academic conferences.

Вмешательства

• Препарат Epirubicin (E)
  Epirubicin is administered via transarterial chemoinfusion (TAI) as a neoadjuvant treatment. The drug is delivered at a dose of 60 mg/m² per cycle, diluted in normal saline at a concentration of 1 mg:1 mL. The infusion is performed through super-selective catheterization of the tumor-feeding arteries under angiographic guidance. This cycle is repeated every 4 weeks for a total of 3 cycles prior to response assessment and subsequent stratified local therapy.

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: After completion of 3 cycles (each cycle is 28 days) of interventional chemotherapy (at the time of response assessment)]
• 2-year Progression-Free Survival (PFS) rate [Срок оценки: 2 years from the start of intervention]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From the first dose of interventional chemotherapy up to 30 days after the last dose (approximately 18 weeks)]

Вторичные конечные точки (4)

• Complete Response (CR) Rate [Срок оценки: After completion of 3 cycles ((each cycle is 28 days) ) of interventional chemotherapy (at the time of response assessment)]
• Incidence of Adverse Events related to Surgery and Radiotherapy [Срок оценки: From the start of surgery or radiotherapy until 90 days after completion of local therapy]
• Overall Survival (OS) [Срок оценки: From the start of intervention, assessed up to 5 years]
• Correlation of Biomarker with Treatment Response [Срок оценки: Tissue obtained at baseline (pre-treatment); response assessed after 3 cycles (each cycle is 28 days) of chemotherapy]

Критерии участия

Критерии включения

• Age between 18 and 70 years.
• Histologically confirmed diagnosis of sinonasal adenoid cystic carcinoma (ACC).
• Tumor stage T3 or T4 according to the AJCC (American Joint Committee on Cancer) 8th edition staging system. Participants with lymph node metastasis must be amenable to surgical dissection. Those with distant metastasis must have stable disease.
• Ability to provide a sufficient volume (≥0.5 cm³) of fresh tumor tissue via biopsy or surgery for research purposes, with participant's informed consent.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0 to 2.
• Voluntary participation and provision of written informed consent. Good compliance, able to cooperate with treatment and follow-up.

Критерии исключения

• Prior treatment with Epirubicin or any other anthracycline-based chemotherapy.
• Prior radiotherapy to the head and neck region.
• Administration of any other chemotherapy, targeted therapy, or immunotherapy within 4 weeks prior to study enrollment.
• Concurrent participation in another interventional drug clinical trial.
• Inadequate liver, kidney, or bone marrow function that does not meet the requirements for the planned treatment regimen.
• Contraindications to anthracycline-containing chemotherapy regimens: known allergy to anthracyclines, presence of ≥ Grade 2 peripheral neuropathy, or uncontrolled nausea/vomiting or chronic gastrointestinal diseases.
• Severe uncontrolled acute infection or decompensated major organ dysfunction.
• Pregnancy or lactation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Eye and ENT Hospital, Fudan University — Шанхай

Публикации

• Vermorken JB, Verweij J, de Mulder PH, Cognetti F, Clavel M, Rodenhuis S, Kirkpatrick A, Snow GB. Epirubicin in patients with advanced or recurrent adenoid cystic carcinoma of the head and neck: a phase II study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol. 1993 Nov;4(9):785-8. doi: 10.1093/oxfordjournals.annonc.a058665. PMID 8280659
• Zhou J, Yu Z, Wang S, Li N. Practical guideline for recurrent or metastatic adenoid cystic carcinoma. Innovation (Camb). 2025 May 21;6(9):100957. doi: 10.1016/j.xinn.2025.100957. eCollection 2025 Sep 8. No abstract available. PMID 40979299
• Teymoortash A, Zieger L, Hoch S, Pagenstecher A, Hofer MJ. Distinct microscopic features of perineural invasion in adenoid cystic carcinoma of the head and neck. Histopathology. 2014 Jun;64(7):1037-9. doi: 10.1111/his.12210. Epub 2013 Aug 19. No abstract available. PMID 24033920
• van Weert S, van der Waal I, Witte BI, Leemans CR, Bloemena E. Histopathological grading of adenoid cystic carcinoma of the head and neck: analysis of currently used grading systems and proposal for a simplified grading scheme. Oral Oncol. 2015 Jan;51(1):71-6. doi: 10.1016/j.oraloncology.2014.10.007. Epub 2014 Oct 28. PMID 25456010
• Lupinetti AD, Roberts DB, Williams MD, Kupferman ME, Rosenthal DI, Demonte F, El-Naggar A, Weber RS, Hanna EY. Sinonasal adenoid cystic carcinoma: the M. D. Anderson Cancer Center experience. Cancer. 2007 Dec 15;110(12):2726-31. doi: 10.1002/cncr.23096. PMID 17960615
• Mavrikios A, Goudjil F, Beddok A, Zefkili S, Bolle S, Feuvret L, Le Tourneau C, Choussy O, Sauvaget E, Herman P, Dendale R, Calugaru V. Proton therapy and/or helical tomotherapy for locally advanced sinonasal skull base adenoid cystic carcinoma: Focus on experience of the Institut Curie and review of literature. Head Neck. 2023 Jul;45(7):1619-1631. doi: 10.1002/hed.27371. Epub 2023 Apr 25. PMID 37097003
• Bjorndal K, Krogdahl A, Therkildsen MH, Overgaard J, Johansen J, Kristensen CA, Homoe P, Sorensen CH, Andersen E, Bundgaard T, Primdahl H, Lambertsen K, Andersen LJ, Godballe C. Salivary gland carcinoma in Denmark 1990-2005: a national study of incidence, site and histology. Results of the Danish Head and Neck Cancer Group (DAHANCA). Oral Oncol. 2011 Jul;47(7):677-82. doi: 10.1016/j.oraloncology.2 PMID 21612974
• Dodd RL, Slevin NJ. Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol. 2006 Sep;42(8):759-69. doi: 10.1016/j.oraloncology.2006.01.001. Epub 2006 Jun 6. PMID 16757203

Идентификаторы

NCT: NCT07320508 · EyeEntFudan-2025307 · 2025307

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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