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

Official title

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

Overview

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.

Detailed description

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).

Interventions

• Drug 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.
• Drug 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.

Primary outcome measures

• Event-Free Survival (EFS) [Time frame: 3 years from randomization]

Secondary outcome measures (6)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

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

Identifiers

NCT: NCT07463313 · 20251109101922438 · 2026HS060

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗