Neoadjuvant Pimicotinib Combined With Surgery Versus Upfront Surgery for Diffuse Tenosynovial Giant Cell Tumor: A Randomized, Open-label Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Event-free survival
研究概览
简要总结
Tenosynovial giant cell tumor (TGCT) is a rare neoplasm predominantly occurring in young and middle-aged adults, characterized by high recurrence and high disability rates. Surgery represents the first-line treatment at present. Although surgical resection can eradicate lesions, repeated surgical interventions constitute the major disease-related burden. Particularly for patients with diffuse-type TGCT (D-TGCT), postoperative recurrence rates can exceed 50%.
Pimicotinib is a highly selective colony-stimulating factor 1 receptor (CSF1R) inhibitor. The phase III MANEUVER trial has verified its prominent tumor shrinkage effect and symptomatic improvement in patients with unresectable, symptomatic TGCT, with an objective response rate (ORR) of 54%. In addition, pimicotinib demonstrates a favorable safety profile; most adverse events are mild in severity, mainly including pruritus, edema, fatigue and elevated creatine kinase, without severe hepatotoxicity.
Neoadjuvant therapy followed by surgery falls within the scope of multimodal treatment, which is mostly applied to recurrent and refractory cases rather than the standard upfront regimen for treatment-naive patients. Clinical case reports and real-world observations have preliminarily validated the feasibility and clinical value of sequential systemic targeted therapy followed by surgical resection. To date, systematic and standardized clinical data regarding neoadjuvant strategies remain scarce, especially randomized controlled evidence comparing neoadjuvant targeted therapy plus surgery versus primary upfront surgery. This study aims to compare the efficacy and safety of neoadjuvant pimicotinib combined with surgery versus upfront primary surgery in the management of D-TGCT, so as to generate evidence-based rationale for developing more effective and safe therapeutic regimens for D-TGCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged ≥18 years
- •Histologically confirmed tenosynovial giant cell tumor (TGCT)
- •Resectable diffuse tenosynovial giant cell tumor (D-TGCT) were determined by multidisciplinary team (MDT) discussion.
- •Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 with at least one lesion of ≥2 cm
- •Symptomatic disease with a worst pain of at least 4 or/and a worst stiffness of at least 4 (based on a scale of 0-10 with 10 describing the worst condition) prior to randomization Adequate organ and bone marrow function
- •Adequate organ function and bone marrow function
- •Willing and able to complete patient-reported outcome (PRO) assessments throughout the study.
排除标准
- •Prior treatment with highly selective Colony-Stimulating Factor 1 (CSF1)/ Colony-Stimulating Factor 1 Receptor (CSF1R) inhibitors before randomization
- •Presence of another malignancy requiring active treatment, in the investigator's judgment, which may interfere with study participation or results
- •Known metastatic TGCT
- •Severe concomitant arthropathy, severe illness, or uncontrolled infection in the affected joint
- •Significant factors affecting oral drug absorption
- •Concomitant use of strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days before randomization
- •Impaired cardiac function or severe cardiac disease
- •Known active Human Immunodeficiency Virus (HIV) infection, active hepatitis B, active hepatitis C, or active tuberculosis before randomization
- •Known active liver or biliary disease, or other conditions that may cause abnormal liver function tests during the study
- •Pregnant or lactating female (pregnancy defined as from conception until termination)
- •Fertile males or non-sterilized females who do not agree to use effective contraception from at least 14 days before randomization until 6 months after the last dose of study drug
- •Other serious comorbidities that, in the investigator's judgment, may affect protocol compliance, interfere with interpretation of study results, or increase the patient's risk of safety events
结局指标
主要结局
Event-free survival
时间窗: 2 years
Events are defined as disease progression precluding planned surgery, local recurrence, distant metastasis, treatment discontinuation due to adverse events, or death from any cause.
次要结局
- Local recurrence rate(2 year)
- Surgical complication rate(2 years)
- Change in range of motion(2 years)
- Change in Brief Pain Inventory (BPI)(2 years)
- Change in stiffness Numerical Rating Scale (NRS)(2 years)
- Change in Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) score(2 years)