Neoadjuvant Anlotinib and Epirubicin for T4 Sinonasal Adenoid Cystic Carcinoma

NCT07616141 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2026069-1
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

Brief Summary

T4 stage sinonasal adenoid cystic carcinoma (SNACC) is a rare but aggressive cancer in the nasal cavity and sinuses. These tumors often invade the skull base, eye socket, or brain covering (dura), making complete surgical removal difficult and carrying a high risk of recurrence even after surgery and radiation. The goal of this study is to test whether a new combination of drugs given before surgery - anlotinib (a targeted therapy) plus epirubicin (a chemotherapy drug) - can improve outcomes for patients with T4 SNACC. This is a prospective, multicenter, single-arm, phase II clinical trial. Eligible participants will receive 2 cycles of neoadjuvant treatment (anlotinib orally for 2 weeks on/1 week off, plus epirubicin intravenously on day 1 of each 3-week cycle). After completing neoadjuvant therapy, participants will undergo surgery to remove the tumor, followed by postoperative radiotherapy. The main question the study tries to answer is whether this approach increases the 3-year progression-free survival (PFS) rate compared to the historical rate of about 70% with standard treatment (surgery plus radiotherapy alone). Secondary questions include how many tumors shrink after neoadjuvant treatment, how many operations achieve complete removal with negative margins, major pathological response rates, overall survival, safety, quality of life, and the chance of avoiding disfiguring surgeries (such as removal of the eye or part of the skull). The study will enroll about 76 participants from 5 top medical centers in China. If positive, this study may establish a new standard of care for T4 SNACC.

Conditions

Adenoid Cystic Carcinoma

Keywords

Adenoid Cystic Carcinoma; Sinonasal; T4 Stage; Neoadjuvant Therapy; Anlotinib; Epirubicin; Prospective Study; Phase II Clinical Trial

Outcome Measures

Primary Outcomes (1)

• 3-Year Progression-Free Survival

  Progression-free survival (PFS) is defined as the time from enrollment to the first documentation of disease progression (local recurrence, regional recurrence, or distant metastasis) or death from any cause, whichever occurs first. The 3-year PFS rate is the proportion of participants who remain alive and free from disease progression at 3 years after enrollment.

  From enrollment to 3 years post-enrollment (assessed every 3 months for the first 2 years, then every 6 months) or until progression or death

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  At week 6 (after completion of 2 cycles of neoadjuvant therapy, before surgery)

• R0 Resection Rate

  At time of surgery (approximately week 10-12 after enrollment)

• Overall Survival

  From enrollment up to 5 years (assessed every 3 months for first 2 years, then every 6 months)

• Local Control Rate

  At 1 year, 2 years, and 3 years post-enrollment

• Adverse events

  From first dose of study drug until 30 days after last dose or surgery, whichever is later

Study Arms (1)

Neoadjuvant Anlotinib + Epirubicin

EXPERIMENTAL

Participants receive neoadjuvant therapy for 2 cycles (each cycle is 21 days). Anlotinib 10 mg orally once daily on days 1-14 (2 weeks on, 1 week off). Epirubicin 70 mg/m² intravenous infusion on day 1 of each cycle. After completion of neoadjuvant therapy, participants undergo radical surgery followed by postoperative radiotherapy as per protocol.

Drug: Anlotinib + Epirubicin

Interventions

Anlotinib + Epirubicin DRUG

Anlotinib 10 mg orally once daily on days 1-14 of each 21-day cycle (2 weeks on, 1 week off) for 2 cycles.

Neoadjuvant Anlotinib + Epirubicin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years, any sex.
• Histopathologically confirmed sinonasal adenoid cystic carcinoma (any subtype).
• Stage T4a or T4b according to AJCC 8th edition. If lymph node metastasis is present, it must be surgically resectable. If distant metastasis is present, metastatic lesions must be stable.
• Multidisciplinary team (MDT) assessment confirms that the tumor is technically resectable but with high risk (invasion of skull base, orbit, dura, etc.).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate bone marrow, liver, kidney, and cardiac function: absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L; ALT/AST ≤2.5×upper limit of normal (ULN), total bilirubin ≤1.5×ULN; creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min; left ventricular ejection fraction (LVEF) ≥50%.
• Willing to participate and able to provide written informed consent (including for clinical treatment and translational research).

You may not qualify if:

• Prior radiotherapy to the head and neck region.
• Prior anthracycline therapy with cumulative dose ≥300 mg/m².
• Known hypersensitivity to any component of anlotinib or epirubicin.
• Uncontrolled hypertension, severe cardiovascular disease, or active infection.
• Pregnant or breastfeeding women.
• Any medical or psychosocial condition that, in the investigator's judgment, may interfere with study compliance or conduct.

Sponsors & Collaborators

• Eye & ENT Hospital of Fudan University: lead

Study Sites (5)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266000, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200030, China

Location

Eye & ENT Hospital of Fudan University

Shanghai, Shanghai Municipality, 200031, China

Location

Related Publications (10)

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  PMID: 37643133 RESULT

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  PMID: 17960615 RESULT

• Michel G, Joubert M, Delemazure AS, Espitalier F, Durand N, Malard O. Adenoid cystic carcinoma of the paranasal sinuses: retrospective series and review of the literature. Eur Ann Otorhinolaryngol Head Neck Dis. 2013 Nov;130(5):257-62. doi: 10.1016/j.anorl.2012.09.010. Epub 2013 Jun 6.

  PMID: 23747147 RESULT

• Song X, Sun J, Yang G, Wang X, Wang L. Long-term outcomes of platinum-based chemotherapy for T4 stage sinonasal adenoid cystic carcinoma. Front Pharmacol. 2025 Sep 29;16:1623242. doi: 10.3389/fphar.2025.1623242. eCollection 2025.

  PMID: 41089828 RESULT

• Mauthe T, Holzmann D, Soyka MB, Mueller SA, Balermpas P, Held U, Freiberger SN, Rupp NJ, Meerwein CM. Overall and disease-specific survival of sinonasal adenoid cystic carcinoma: a systematic review and meta-analysis. Rhinology. 2023 Dec 1;61(6):508-518. doi: 10.4193/Rhin23.204.

  PMID: 37703531 RESULT

• Cavalieri S, Mariani L, Vander Poorten V, Van Breda L, Cau MC, Lo Vullo S, Alfieri S, Resteghini C, Bergamini C, Orlandi E, Calareso G, Clement P, Hauben E, Platini F, Bossi P, Licitra L, Locati LD. Prognostic nomogram in patients with metastatic adenoid cystic carcinoma of the salivary glands. Eur J Cancer. 2020 Sep;136:35-42. doi: 10.1016/j.ejca.2020.05.013. Epub 2020 Jul 3.

  PMID: 32629365 RESULT

• Seok J, Lee DY, Kim WS, Jeong WJ, Chung EJ, Jung YH, Kwon SK, Kwon TK, Sung MW, Ahn SH. Lung metastasis in adenoid cystic carcinoma of the head and neck. Head Neck. 2019 Nov;41(11):3976-3983. doi: 10.1002/hed.25942. Epub 2019 Aug 29.

  PMID: 31463986 RESULT

• 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 RESULT

• 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.2011.04.020. Epub 2011 May 25.

  PMID: 21612974 RESULT

• 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 RESULT

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

anlotinib; Epirubicin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Quan Liu, MD

CONTACT

+86 15001959681; liuqent@163.com

Wanpeng Li, MD

CONTACT

+86 13262856870; 18879117831@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Interventional Study Model

Study Record Dates

• First Submitted: May 17, 2026
• First Posted: June 1, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)