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

Phase 3Not Yet RecruitingNCT07463313

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine116 enrolled

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.

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).

Study Type

INTERVENTIONAL

Allocation

Interventions

Cyclophosphamide, Doxorubicin, and Cisplatin (CAP)DRUG

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.

nab-Paclitaxel and CarboplatinDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Event-Free Survival (EFS)

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.

Time frame: 3 years from randomization

Secondary Outcomes

Objective Response Rate (ORR)

Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1 criteria after neoadjuvant chemotherapy.

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

Proportion of participants who remain free of events (disease progression, incomplete resection, recurrence, or death) at 3 years after randomization.

Time frame: 3 years from randomization

R0 Resection Rate

Proportion of participants achieving complete (R0) resection, defined as microscopically negative surgical margins at the time of surgery.

Time frame: At the time of surgery

Pathological Complete Response (pCR) Rate

Proportion of participants achieving pathological complete response (pCR), defined as no viable tumor cells in the surgical resection specimen, as assessed by central pathology review.

Time frame: At the time of surgery

Major Pathological Response (MPR) Rate

Proportion of participants achieving major pathological response (MPR), defined as ≤10% residual viable tumor cells in the surgical resection specimen, as assessed by central pathology review.

Time frame: At the time of surgery

Incidence and Severity of Adverse Events

Incidence, nature, and severity of adverse events and serious adverse events as assessed by NCI CTCAE v5.0, including hematologic toxicity, non-hematologic toxicity, and treatment-related deaths.

Time frame: Throughout the study, from first dose to 30 days after last dose of chemotherapy

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts