Thymoma and Thymic Carcinoma
Conditions
Keywords
Neoadjuvant Chemotherapy, Thymic Epithelial Tumor, Thymic Carcinoma, Event-Free Survival, Mediastinal Tumor
Brief summary
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
DRUGCyclophosphamide, 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.
DRUGnab-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.
Sponsors
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | After completion of neoadjuvant chemotherapy (approximately 9 weeks for 3-cycle arm; approximately 18 weeks for 6-cycle arm) | Proportion of participants achieving complete response (CR) or partial response (PR) per RECIST v1.1 criteria after neoadjuvant chemotherapy. |
| 3-Year Event-Free Survival Rate | 3 years from randomization | Proportion of participants who remain free of events (disease progression, incomplete resection, recurrence, or death) at 3 years after randomization. |
| R0 Resection Rate | At the time of surgery | Proportion of participants achieving complete (R0) resection, defined as microscopically negative surgical margins at the time of surgery. |
| Pathological Complete Response (pCR) Rate | At the time of surgery | 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. |
| Major Pathological Response (MPR) Rate | At the time of surgery | 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. |
| Incidence and Severity of Adverse Events | Throughout the study, from first dose to 30 days after last dose of chemotherapy | 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. |
Countries
China
Contacts
CONTACTFan Jiang, MD, PhD
PRINCIPAL_INVESTIGATORFan Jiang, MD, PhD
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed