Clinical trial NCT06924619: Neoadjuvant Radiotherapy for Locally Advanced Unresectable Thymoma
Official title: A Prospective, Randomized, Controlled Phase Ⅱ Clinical Trial of Neoadjuvant Radiotherapy for Locally Advanced Unresectable Thymoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Thymoma
Keywords: neoadjuvant radiotherapy
Locally Advanced Thymoma
neoadjuvant chemoradiotherapy
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2025-04-11
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this prospective, randomized, controlled phase II clinical study is to evaluate the efficacy and safety of neoadjuvant radiotherapy in patients with locally advanced unresectable thymoma. The main questions it aims to answer are:

1. Which treatment method is more effective in improving the radical resection rate: neoadjuvant chemoradiotherapy or neoadjuvant radiotherapy ?
2. The safety and adverse reactions of neoadjuvant radiotherapy? Does the addition of neoadjuvant chemotherapy have an impact on this?

Participants will be randomly divided into two groups: one group will receive neoadjuvant radiotherapy, and the other will receive neoadjuvant chemoradiotherapy. The primary endpoint of the study is to evaluate the radical resection rate (R0) of two groups. The secondary endpoints will include the pathological complete response rate (pCR), 3-year progression-free survival, and safety and toxicities. In addition, this study will explore the feasibility and completion rate of minimally invasive surgical resection.

Detailed description: For patients with thymoma, surgery is the optimal choice, and it has been proven to improve the survival rate of patients with thymoma. For locally advanced unresectable thymoma, direct surgical resection is associated with significant trauma, a high incidence of surgical complications, and a risk of postoperative recurrence. The application of neoadjuvant therapy is expected to reduce tumor volume and downstage the tumor, thereby increasing the rate of complete tumor resection (R0). Clinical practice has confirmed that thymic tumors are sensitive to both radiotherapy and chemotherapy. However, neoadjuvant chemotherapy regimens for thymoma have not been unified, and the available evidence recommends cisplatin based combination regimens. Earlier retrospective studies mainly targeting locally advanced unresectable thymoma suggested that neoadjuvant radiotherapy could achieve an R0 resection rate of about 50%-75% in these patients. In recent years, neoadjuvant chemoradiotherapy has shown promise in terms of objective response rate and R0 resection rate in patients with thymoma. There is still controversy over how to choose an appropriate neoadjuvant treatment protocol for such patients, and there is a lack of randomized prospective controlled studies.

In this prospective randomized controlled study, participants will be randomly assigned in a 1:1 ratio into two groups. One group will receive neoadjuvant radiotherapy alone, while the other group will receive the same radiotherapy regimen in combination with concurrent cisplatin chemotherapy. Participants in both groups will undergo standard surgery based on efficacy assessment. The purpose of this study is to evaluate the impact of these two approaches on the R0 resection rate in patients and to comprehensively assess the safety of the treatment modalities. This study also aims to provide clinical evidence for neoadjuvant treatment strategies in locally advanced unresectable thymoma.

Eligibility criteria: Inclusion Criteria:

* Aged ≥18 years and ≤75 years.
* Histologically confirmed thymoma of Masaoka-Koga stage III-IV A.
* Assessed as unresectable thymoma by a thoracic surgeon prior to treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* No prior anti-thymoma treatment, including but not limited to systemic chemotherapy, radiotherapy, surgery, or immunotherapy.
* Presence of at least one measurable lesion according to RECIST v1.1 criteria.
* Cardiopulmonary function compatible with surgery.
* Expected survival of \>3 months.
* Comprehensive evaluation completed within 28 days before enrollment in the study, with a full blood cell test obtained within 15 days, demonstrating normal visceral organ function and normal bone marrow function.
* Negative serum or urine pregnancy test for women of childbearing potential within 14 days before study enrollment.
* Willingness of the patient to sign an informed consent form and to adhere to the specified follow-up schedule.

Exclusion Criteria:

* Histologically confirmed thymic neuroendocrine tumor.
* Currently participating in an interventional clinical study that may affect this study, or having received other investigational drugs or devices within 4 weeks prior to the first treatment in this study.
* Pregnant or breastfeeding women.
* Previous history of thoracic radiotherapy.
* Deemed unsuitable for three-dimensional conformal or intensity-modulated radiotherapy by a radiation oncology specialist.
* History of allogeneic bone marrow or organ transplantation.
* History of malignancies other than thymoma within the past 3 years, or untreated other primary malignancies.
* Serious comorbidities that would affect the study treatment.
* Any history or evidence of disease, treatment, or abnormal laboratory values that could interfere with the study results or prevent the participant from completing the study, or other situations deemed unsuitable for enrollment by the investigator.

Primary outcomes:
measure: Radical resection rate（R0）
timeFrame: up to 1 year
Secondary outcomes:
measure: pCR rate
timeFrame: up to 1 year
measure: PFS
timeFrame: up to 3 years
measure: Safety and toxicities
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
References: