6 vs 3 Cycles of Neoadjuvant Chemotherapy for Potentially Resectable Locally Advanced Thymic Epithelial Tumors

Официальное название

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

Обзор

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.

Подробное описание

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

Imaging assessment (RECIST 1.1) every 2 cycles. CR/PR: proceed to surgery; SD: continue chemotherapy; PD: radical radiotherapy.

Post-operative radiotherapy as indicated (R0: 45-50 Gy; R1: 54 Gy; R2: 60-70 Gy).

Primary endpoint: Event-Free Survival (EFS), defined as time from randomization to first occurrence of tumor recurrence, progression, or death.

Sample size: 116 patients (58 per arm), based on ORR comparison (25% vs 50%, α=0.05, power=0.80, 5% dropout/year).

Follow-up: 3 years post-enrollment (total study duration 6 years).

Вмешательства

• Препарат Cyclophosphamide, Doxorubicin, and Cisplatin (CAP)
  Chemotherapy regimen for WHO type B thymoma. Cyclophosphamide 500 mg/m2 IV + Doxorubicin 50 mg/m2 IV + Cisplatin 50 mg/m2 IV, administered every 3 weeks. Experimental arm receives 6 cycles; Control arm receives 3 cycles prior to surgery.
• Препарат nab-Paclitaxel and Carboplatin
  Chemotherapy regimen for thymic carcinoma. nab-Paclitaxel 260 mg/m2 IV + Carboplatin AUC 5 IV, administered every 3 weeks. Experimental arm receives 6 cycles; Control arm receives 3 cycles prior to surgery.

Первичные конечные точки

• Event-Free Survival (EFS) [Срок оценки: 3 years from randomization]

Вторичные конечные точки (6)

• Objective Response Rate (ORR) [Срок оценки: 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 [Срок оценки: 3 years from randomization]
• R0 Resection Rate [Срок оценки: At the time of surgery]
• Pathological Complete Response (pCR) Rate [Срок оценки: At the time of surgery]
• Major Pathological Response (MPR) Rate [Срок оценки: At the time of surgery]
• Incidence and Severity of Adverse Events [Срок оценки: Throughout the study, from first dose to 30 days after last dose of chemotherapy]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07463313 · 20251109101922438 · 2026HS060

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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