A Phase IB Study to Assess Safety of Concurrent Azeliragon With Craniospinal Irradiation in Patients With Leptomeningeal Metastasis From Solid Tumor Malignancies or High-Grade Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Number of Patients with Dose-Limiting Toxicities (DLTs) at Dose Level 1
研究概览
简要总结
Single institution study to assess the safety of concurrent Azeliragon with craniospinal irradiation (CSI) in patients with leptomeningeal metastasis from solid tumor malignancies and high-grade gliomas.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with solid tumor malignancy or high grade glioma with leptomeningeal metastasis established radiographically and/or through cerebrospinal fluid (CSF) cytology
- •Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastasis
- •Patients with Karnofsky Performance Status of 60 or greater.
- •Male or non-pregnant and non-lactating female and ≥ 18 years of age.
- •Patients with absolute neutrophil count (ANC) ≥ 1.0 × 109/L, platelet count ≥ 75,000/mm3 (75 × 109/L), and hemoglobin (Hgb) ≥ 8 g/dL. Transfusion or growth factor support is allowed.
- •Patients with aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase(SGOT)], alanine aminotransferase (ALT) [serum glutamic-pyruvic transaminase (SGPT)] ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 x ULN is acceptable, total bilirubin ≤ 1.5 × ULN, and estimated creatinine clearance of > 30 mL/min (per Cockroft-Gault formula).
- •Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.
排除标准
- •Patient has a life expectancy, per investigator assessment, of less than 2 months.
- •Patients unable to complete the English quality of life questionnaires
- •Patient with extensive systemic disease and who declined standard systemic treatment options
- •Patient who is unable to undergo magnetic resonance imaging (MRI) brain and spine with gadolinium contrast
- •Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerance
- •Active, uncontrolled bacterial, or fungal infection(s) requiring systemic therapy.
- •Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity.
- •Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication.
- •Patients with a gastrointestinal condition that could interfere with swallowing or absorption.
- •Females of childbearing potential who are sexually active or males with female partners of childbearing potential, where either the female or the male is unwilling to use a highly effective method of contraception during the trial and for 6 months after the last administration of study drug.
- •Pregnant or lactating women
研究组 & 干预措施
Dose Determination followed by Dose Expansion
Patients with leptomeningeal metastasis from a solid tumor or primary CNS high-grade glioma will be enrolled and start Azeliragon 7 days prior to CSI, during CSI, and for 7 days days after completion of CSI (Dose Determination). Patients will be monitored for dose limiting toxicities during protocol therapy.
Once the recommended dose is identified, additional patients will be treated with Azeliragon at recommended dose in combination with craniospinal irradiation (Dose Expansion).
干预措施: CSI (Procedure)
Dose Determination followed by Dose Expansion
Patients with leptomeningeal metastasis from a solid tumor or primary CNS high-grade glioma will be enrolled and start Azeliragon 7 days prior to CSI, during CSI, and for 7 days days after completion of CSI (Dose Determination). Patients will be monitored for dose limiting toxicities during protocol therapy.
Once the recommended dose is identified, additional patients will be treated with Azeliragon at recommended dose in combination with craniospinal irradiation (Dose Expansion).
干预措施: Azeliragon (Drug)
结局指标
主要结局
Number of Patients with Dose-Limiting Toxicities (DLTs) at Dose Level 1
时间窗: Up to Week 4
DLTs assess using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
Number of Patients with DLTs at Dose Level -1
时间窗: Up to Week 4
DLTs assess using CTCAE v 5.0.
Number of Patients with DLTs at Dose Level -2
时间窗: Up to Week 4
DLTs assess using CTCAE v 5.0.
次要结局
- Central nervous system (CNS) progression-free survival (PFS)(Up to Month 13 (12 Months Post-Protocol Therapy))
- Overall Survival (OS)(Up to Month 13 (12 Months Post-Protocol Therapy))