Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Trastuzumab Via the Ommaya Reservoir in Breast Cancer With Leptomeningeal Metastasis: a Phase II Multicenter Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Intracranial Overall Response Rate
研究概览
简要总结
Evaluate the efficacy and safety of Intrathecal Administration of Thiotepa in Combination with Trastuzumab via the Ommaya Reservoir in Breast Cancer with Leptomeningeal Metastasis
详细描述
This was a II, single-arm, prospective, multicenter study designed to estimate the efficacy and safety of intrathecal administration of thiotepa in combination with Trastuzumab via the Ommaya Reservoir in HER2-positive breast cancer with leptomeningeal metastasis.
The primary end point was iORR [complete response (CR) + partial response (PR)] according to RANO-LM. Scoring based on radiographic assessment in leptomeningeal metastases . A composite score (total score) is calculated and compared with the baseline total score. A 25% worsening in the current score relative to baseline defines radiographic progressive disease. A 50% improvement in the current score defines a radiographic partial response. Resolution of all baseline radiographic abnormalities defines a complete response. All other situations define stable disease. The secondary end points were changes in iPFS,PFS, OS, and exploratory analysis of the relationship between molecular markers and therapeutic efficacy.
This study is planned to include 26 patients with leptomeningeal metastasis from breast cancer who meet the entry criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •The subjects must meet all of the following criteria simultaneously:
- •Histologically or cytologically confirmed HER-2 positive breast cancer (immunohistochemistry indicates HER-2 3+ and/or fluorescence in situ hybridization indicates HER-2 gene amplification)
- •Diagnosed with breast cancer with leptomeningeal metastasis based on cerebrospinal fluid cytology combined with central nervous system function and brain imaging findings
- •The patient has an Ommaya reservoir implanted or is eligible for implantation
- •Adequate bone marrow and liver and kidney function reserves: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 90 g/L. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. Total serum bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome can be enrolled if total bilirubin < 3 x ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; if the patient has liver metastasis, this criterion is AST and ALT ≤ 5 x ULN.
- •Female, aged between 18 and 75 years old
- •Left ventricular ejection fraction (LVEF) > 50%
- •Voluntary signing of informed consent form
排除标准
- •Patients meeting any of the following criteria are not eligible to be included in this study:
- •Subjects with other malignant tumors, excluding skin basal cell carcinoma and carcinoma in situ
- •Presence of severe or uncontrollable systemic diseases, including uncontrollable hypertension or active bleeding tendency
- •Patients judged by the investigator to be unsuitable for participation in the trial, or those with factors that may affect the patient's compliance with the protocol
- •Toxicity caused by previous treatment has not recovered to normal state or is grade 1 according to NCI-CTCAE 5.0
- •Allergic to or with metabolic disorders to the drugs in this protocol
- •Pregnant or lactating women, or women with pregnancy plans during the study period and within 6 months after the last administration
- •Patients participating in other clinical studies simultaneously
研究组 & 干预措施
Experimental
Intrathecal chemotherapy group Patients received intrathecal 150mg Trastuzumab combination with 10mg thiotepa once every three weeks until an event that meets the criteria for termination occurs.
干预措施: Intrathecal Administration of Thiotepa in Combination with Trastuzumab via the Ommaya Reservoir (Drug)
结局指标
主要结局
Intracranial Overall Response Rate
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Intracranial overall response rate (iORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RANO-LM.
次要结局
- Intracranial Progression Free Survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Progression Free Survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Overall Survival(From date of randomization until the date of death from any cause, assessed up to 100 months)
- frequency/severity of adverse events, lab abnormalities(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)