Adenoid Cystic Carcinoma, Sinonasal Carcinoma, Epirubicin
Conditions
Keywords
transarterial chemoembolization, objective response rate, 2-year progression-free surviva
Brief summary
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.
Detailed description
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.
Interventions
DRUGEpirubicin (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.
Sponsors
Eye & ENT Hospital of Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. The assignment to subsequent local therapy is based on objective imaging assessment (RECIST 1.1).
Intervention model description
This is a single-arm, response-adapted study. All enrolled participants will first receive the same interventional chemotherapy. After central imaging assessment, they will be assigned to one of two predefined, stratified local therapy pathways based on their objective tumor response (complete response or not), as per protocol.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 70 years. 2. Histologically confirmed diagnosis of sinonasal adenoid cystic carcinoma (ACC). 3. Tumor stage T3 or T4 according to the AJCC (American Joint Committee on Cancer) 9th edition staging system. Participants with lymph node metastasis must be amenable to surgical dissection. Those with distant metastasis must have stable disease. 4. 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. 5. ECOG (Eastern Cooperative Oncology Group) performance status score of 0 to 2. 6. Voluntary participation and provision of written informed consent. Good compliance, able to cooperate with treatment and follow-up.
Exclusion criteria
1. Prior treatment with Epirubicin or any other anthracycline-based chemotherapy. 2. Prior radiotherapy to the head and neck region. 3. Administration of any other chemotherapy, targeted therapy, or immunotherapy within 4 weeks prior to study enrollment. 4. Concurrent participation in another interventional drug clinical trial. 5. Inadequate liver, kidney, or bone marrow function that does not meet the requirements for the planned treatment regimen. 6. Contraindications to anthracycline-containing chemotherapy regimens: known allergy to anthracyclines, presence of ≥ Grade 2 peripheral neuropathy, or uncontrolled nausea/vomiting or chronic gastrointestinal diseases. 7. Severe uncontrolled acute infection or decompensated major organ dysfunction. 8. Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | After completion of 3 cycles (each cycle is 28 days) of interventional chemotherapy (at the time of response assessment) | The proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria, as assessed by central imaging review after completion of interventional chemotherapy. |
| 2-year Progression-Free Survival (PFS) rate | 2 years from the start of intervention | The proportion of participants alive without disease progression (local recurrence or distant metastasis) at 2 years from the initiation of interventional chemotherapy. Progression is defined per RECIST 1.1 criteria. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From the first dose of interventional chemotherapy up to 30 days after the last dose (approximately 18 weeks) | The frequency and severity of adverse events assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, specifically related to the interventional chemotherapy phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | After completion of 3 cycles ((each cycle is 28 days) ) of interventional chemotherapy (at the time of response assessment) | The proportion of participants achieving complete response (CR) according to RECIST 1.1 criteria, as assessed by central imaging review after completion of interventional chemotherapy. |
| Incidence of Adverse Events related to Surgery and Radiotherapy | From the start of surgery or radiotherapy until 90 days after completion of local therapy | The frequency and severity of adverse events assessed as per CTCAE v5.0, that are attributable to the subsequent local therapy (surgery and/or radiotherapy) phase of the integrated treatment. |
| Overall Survival (OS) | From the start of intervention, assessed up to 5 years | The time from the initiation of interventional chemotherapy to death from any cause. |
| Correlation of Biomarker with Treatment Response | Tissue obtained at baseline (pre-treatment); response assessed after 3 cycles (each cycle is 28 days) of chemotherapy | An exploratory analysis to assess the association between molecular characteristics (e.g., from tumor tissue) and objective response to Epirubicin interventional chemotherapy. |
Countries
China
Contacts
CONTACTQuan Liu, M.D.
CONTACTWanpeng Li, M.D.
PRINCIPAL_INVESTIGATORQuan Liu, M.D.
Eye and ENT Hospital, Fudan University
Outcome results
None listed