A Randomized Controlled Trial of 6 Versus 3 Cycles of Neoadjuvant Chemotherapy on Event-Free Survival in Patients With Potentially Resectable Locally Advanced Thymic Epithelial Tumors
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
This randomized controlled trial compares 6 versus 3 cycles of neoadjuvant chemotherapy in patients with potentially resectable locally advanced thymic epithelial tumors (TETs, WHO type AB/B/C, AJCC TNM stage IIIA-IVA). Patients are randomized 1:1 to receive either 6 or 3 cycles of chemotherapy (cisplatin + doxorubicin + cyclophosphamide for type B; nab-paclitaxel + carboplatin for type C thymoma/thymic carcinoma) every 3 weeks, followed by surgical resection when feasible. The primary endpoint is event-free survival (EFS). The study aims to determine whether extended neoadjuvant chemotherapy improves surgical outcomes and long-term survival in this rare malignancy.
详细描述
Thymic epithelial tumors (TETs) are rare mediastinal malignancies. Locally advanced, potentially resectable TETs present a significant clinical challenge, with limited prospective data on optimal neoadjuvant chemotherapy duration. Retrospective data from Shanghai General Hospital suggest that 6 cycles of neoadjuvant chemotherapy may yield higher objective response rates (75% vs 33.3%) and R0 resection rates (68.75% vs 33.33%) compared to 3 cycles.
This is a single-center, prospective, open-label, randomized controlled trial. Eligible patients are adults (18-65 years) with histologically confirmed WHO type AB, B1, B2, B3 thymoma or thymic carcinoma (type C), AJCC TNM stage IIIA-IVA, deemed potentially resectable by multidisciplinary team (MDT) evaluation, ECOG PS 0-1, with adequate organ function, no prior anti-tumor therapy.
Randomization: 1:1, stratified by histological subtype (type B vs type C), using central randomization with block size 4.
Treatment:
- Type B thymoma arm: cisplatin 50 mg/m² + doxorubicin 50 mg/m² + cyclophosphamide 500 mg/m², Q3W
- Type C thymic carcinoma arm: nab-paclitaxel 200 mg/m² + carboplatin AUC 5, Q3W
- Control group: 3 cycles; Experimental group: 6 cycles
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed thymic epithelial tumor (thymoma or thymic carcinoma)
- •Locally advanced, potentially resectable disease (Masaoka-Koga stage III or IVA), as evaluated by a multidisciplinary team (MDT) including thoracic surgery and thoracic oncology
- •Age 18 to 65 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L
- •Adequate liver function: total bilirubin ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN
- •Adequate renal function: creatinine clearance ≥50 mL/min (Cockcroft-Gault formula)
- •No prior systemic anticancer therapy for thymic epithelial tumor
- •At least one measurable lesion per RECIST v1.1
- •Willing to accept randomization and able to comply with study procedures
- •Written informed consent obtained prior to any study-related procedures
排除标准
- •Prior chemotherapy, targeted therapy, or immunotherapy for thymic epithelial tumor
- •Prior thoracic radiation therapy
- •Active autoimmune disease requiring systemic treatment within the past 2 years
- •Known hypersensitivity or contraindication to study drugs (cisplatin, epirubicin, etoposide, ifosfamide, or any component of these formulations)
- •Severe cardiac dysfunction: New York Heart Association (NYHA) class III or IV heart failure, or left ventricular ejection fraction (LVEF) <50%
- •Active hepatitis B (HBsAg positive with HBV DNA ≥2000 IU/mL), active hepatitis C, or known HIV infection
- •Pregnancy or lactation; women of childbearing potential unwilling to use adequate contraception
- •Other malignancy within 5 years prior to enrollment, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
- •Uncontrolled active infection requiring systemic therapy
- •Any condition that, in the investigator's judgment, would preclude safe participation in the study
研究组 & 干预措施
6-Cycle Neoadjuvant Chemotherapy
Participants receive 6 cycles of neoadjuvant chemotherapy prior to surgery. For WHO type B thymoma: cyclophosphamide 500 mg/m2 IV + doxorubicin 50 mg/m2 IV + cisplatin 50 mg/m2 IV (CAP regimen), every 3 weeks. For thymic carcinoma: nab-paclitaxel 260 mg/m2 IV + carboplatin AUC 5 IV, every 3 weeks.
干预措施: Cyclophosphamide, Doxorubicin, and Cisplatin (CAP) (Drug)
6-Cycle Neoadjuvant Chemotherapy
Participants receive 6 cycles of neoadjuvant chemotherapy prior to surgery. For WHO type B thymoma: cyclophosphamide 500 mg/m2 IV + doxorubicin 50 mg/m2 IV + cisplatin 50 mg/m2 IV (CAP regimen), every 3 weeks. For thymic carcinoma: nab-paclitaxel 260 mg/m2 IV + carboplatin AUC 5 IV, every 3 weeks.
干预措施: nab-Paclitaxel and Carboplatin (Drug)
3-Cycle Neoadjuvant Chemotherapy
Participants receive 3 cycles of neoadjuvant chemotherapy prior to surgery. For WHO type B thymoma: cyclophosphamide 500 mg/m2 IV + doxorubicin 50 mg/m2 IV + cisplatin 50 mg/m2 IV (CAP regimen), every 3 weeks. For thymic carcinoma: nab-paclitaxel 260 mg/m2 IV + carboplatin AUC 5 IV, every 3 weeks.
干预措施: Cyclophosphamide, Doxorubicin, and Cisplatin (CAP) (Drug)
3-Cycle Neoadjuvant Chemotherapy
Participants receive 3 cycles of neoadjuvant chemotherapy prior to surgery. For WHO type B thymoma: cyclophosphamide 500 mg/m2 IV + doxorubicin 50 mg/m2 IV + cisplatin 50 mg/m2 IV (CAP regimen), every 3 weeks. For thymic carcinoma: nab-paclitaxel 260 mg/m2 IV + carboplatin AUC 5 IV, every 3 weeks.
干预措施: nab-Paclitaxel and Carboplatin (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: 3 years from randomization
EFS is defined as the time from randomization to the first occurrence of any of the following events: disease progression precluding surgery, incomplete resection (R1/R2), local or distant recurrence after surgery, or death from any cause.
次要结局
- Objective Response Rate (ORR)(After completion of neoadjuvant chemotherapy (approximately 9 weeks for 3-cycle arm; approximately 18 weeks for 6-cycle arm))
- 3-Year Event-Free Survival Rate(3 years from randomization)
- R0 Resection Rate(At the time of surgery)
- Pathological Complete Response (pCR) Rate(At the time of surgery)
- Major Pathological Response (MPR) Rate(At the time of surgery)
- Incidence and Severity of Adverse Events(Throughout the study, from first dose to 30 days after last dose of chemotherapy)
研究者
Jiang Fan
Chief of Thoracic Surgery
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine