A Prospective, Multicenter Study of Transarterial Epirubicin Chemotherapy in the Treatment of Sinonasal Adenoid Cystic Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
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.
详细描述
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study. The assignment to subsequent local therapy is based on objective imaging assessment (RECIST 1.1).
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Voluntary participation and provision of written informed consent. Good compliance, able to cooperate with treatment and follow-up.
排除标准
- •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.
研究组 & 干预措施
Interventional Chemotherapy with Epirubicin
All participants in this single-arm study will undergo three cycles of transarterial Epirubicin chemoinfusion (60mg/m² per cycle, every 4 weeks) as the initial intervention. Following this, the imaging assessment (MRI, RECIST 1.1) will be performed. Participants will then be assigned to one of two predefined local therapy pathways based on their tumor response: those not achieving a complete response (CR) will undergo skull base surgery followed by radiotherapy; those achieving CR will receive definitive radiotherapy alone.
干预措施: Epirubicin (E) (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: 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.
Objective Response Rate (ORR)
时间窗: 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
时间窗: 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.
次要结局
- Overall Survival (OS)(From the start of intervention, assessed up to 5 years)
- Correlation of Biomarker with Treatment Response(Tissue obtained at baseline (pre-treatment); response assessed after 3 cycles (each cycle is 28 days) of chemotherapy)
- Complete Response (CR) Rate(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(From the start of surgery or radiotherapy until 90 days after completion of local therapy)
研究者
Quan Liu
Senior doctor
Eye & ENT Hospital of Fudan University