Neoadjuvant Anlotinib and Epirubicin for T4 Sinonasal Adenoid Cystic Carcinoma (NAET4-SNACC)

May 23, 2026 updated by: Quan Liu, Eye & ENT Hospital of Fudan University

Neoadjuvant Anlotinib Combined With Epirubicin for T4 Stage Sinonasal Adenoid Cystic Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Clinical Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Sinonasal adenoid cystic carcinoma (SNACC) is a rare cancer. T4 stage tumors often invade the skull base, orbit, or dura, making complete surgical removal difficult. Even with surgery and radiotherapy, the 3-year progression-free survival (PFS) is only about 70%, and extensive resection may cause disfigurement or loss of function.

This is a prospective, multicenter, single-arm, phase II trial. Eligible patients will receive 2 cycles of neoadjuvant therapy (anlotinib 10 mg orally on days 1-14 plus epirubicin 70 mg/m² IV on day 1, 21-day cycle). After neoadjuvant treatment, patients undergo surgery followed by postoperative radiotherapy.

The primary endpoint is 3-year PFS rate, compared with the historical rate of 70%. Secondary endpoints include objective response rate, R0 resection rate, major pathological response, overall survival, safety, quality of life, and organ preservation rate. Exploratory endpoints include biomarkers, ctDNA dynamics, and organoid drug sensitivity.

Target sample size is 76 patients from 5 Chinese centers. The study has been approved by the Institutional Review Board of Eye & ENT Hospital of Fudan University (approval number 2026069-1). Written informed consent will be obtained from all participants.

Study Type

Interventional

Enrollment (Estimated)

76

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100053
        • Xuanwu Hospital, Capital Medical University
        • Contact:
          • Zhenlin Wang, MD
          • Phone Number: 010-83198899 wzl1812@163.com
          • Email: wzl1812@163.com
    • Guangdong
      • Guangzhou, Guangdong, China, 510630
        • The third affiliated hospital of Sun Yat-Sen University
        • Contact:
    • Shandong
      • Qingdao, Shandong, China, 266000
        • The Affiliated Hospital of Qingdao University
        • Contact:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200031
        • Eye & ENT Hospital of Fudan University
        • Contact:
      • Shanghai, Shanghai Municipality, China, 200030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant Anlotinib + Epirubicin
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
Anlotinib 10 mg orally once daily on days 1-14 of each 21-day cycle (2 weeks on, 1 week off) for 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3-Year Progression-Free Survival
Time Frame: 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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: At week 6 (after completion of 2 cycles of neoadjuvant therapy, before surgery)
Proportion of participants achieving complete response (CR) or partial response (PR) after neoadjuvant therapy, assessed by RECIST v1.1 (blinded independent central review).
At week 6 (after completion of 2 cycles of neoadjuvant therapy, before surgery)
R0 Resection Rate
Time Frame: At time of surgery (approximately week 10-12 after enrollment)
Proportion of participants undergoing surgery who achieve microscopically negative margins (no tumor cells at the resection margin on final pathology).
At time of surgery (approximately week 10-12 after enrollment)
Overall Survival
Time Frame: From enrollment up to 5 years (assessed every 3 months for first 2 years, then every 6 months)
Time from enrollment to death from any cause. Participants who are alive at last follow-up will be censored.
From enrollment up to 5 years (assessed every 3 months for first 2 years, then every 6 months)
Local Control Rate
Time Frame: At 1 year, 2 years, and 3 years post-enrollment
Proportion of participants without local recurrence (at primary tumor site) at specified time points.
At 1 year, 2 years, and 3 years post-enrollment
Adverse events
Time Frame: From first dose of study drug until 30 days after last dose or surgery, whichever is later
Incidence, type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs) assessed by CTCAE version 5.0.
From first dose of study drug until 30 days after last dose or surgery, whichever is later
EORTC QLQ-C30
Time Frame: Baseline, at week 6 (after neoadjuvant therapy), at 6 months, 12 months, 24 months, and 36 months post-enrollment
Change from baseline in EORTC QLQ-C30.
Baseline, at week 6 (after neoadjuvant therapy), at 6 months, 12 months, 24 months, and 36 months post-enrollment
Organ Preservation Rate
Time Frame: At time of surgery (approximately week 10-12 after enrollment)
Proportion of participants who avoid disfiguring surgeries including orbital exenteration, maxillectomy, craniotomy, or skull base resection compared to hypothetical initial surgery without neoadjuvant therapy.
At time of surgery (approximately week 10-12 after enrollment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eye & ENT Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2031

Study Registration Dates

First Submitted

May 17, 2026

First Submitted That Met QC Criteria

May 23, 2026

First Posted (Actual)

June 1, 2026

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 23, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026069-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared due to concerns about participant privacy and limitations of informed consent.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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