A Phase I Study of BPM31510 Plus Vitamin K in Subjects With High-Grade Glioma That Has Recurred on a Bevacizumab Containing Regimen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Seema Nagpal
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Percentage of patients with dose-limiting toxicities defined as thrombocytopenia >= grade 3, hemorrhage >= grade 3, and INR elevation >= grade 2 assessed by CTCAE v4.03
研究概览
简要总结
This phase I trial studies the side effects and best dose of ubidecarenone injectable nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma or glioblastoma) that has come back and have been previously treated with bevacizumab. BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
Primary Objective:
- Assess the safety and tolerability of BPM31510 plus vitamin K in subjects with high-grade glioma(HGG), defined as anaplastic astrocytoma (AA) or glioblastoma (GB) that has recurred on a BEV containing regimen.
Secondary Objectives:
- To evaluate plasma pharmacokinetics (PK) when BPM31510 plus vitamin K is given to subjects with HGG recurrent on a BEV containing regimen.
Exploratory Objectives:
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
- •Be ≥ 18 years of age
- •Have a life expectancy ≥ 6 weeks
- •Have a Karnofsky Performance Score (KPS) ≥ 60
- •Have pathologically proven GB, gliosarcoma (WHO IV), or anaplastic astrocytoma (WHO III) in recurrence after treatment with bevacizumab
- •Be at least 14 days from the last administration of bevacizumab
- •Be at least 28 days from last administration of cytotoxic chemotherapy or other investigational agent
- •Have received radiation therapy with concurrent temozolomide. Total radiation dosage can range from 5400 to 6000 cGy administered in daily fractions of 150 to 200 cGy over 6 weeks, or the equivalent in a hypofractionated protocol (for example, 4000cGy in 15 fractions or 2500cGy in 5 fractions). Patients who are MGMT negative do not need to have received temozolomide.
- •Have adequate organ and marrow function as follows (all required):
- •ANC ≥ 1500 mm3
- •Platelets ≥ 100,000/mm3
- •Hemoglobin ≥ 9 g/dL
- •Serum creatinine ≤ 1.8 mg/dL or creatinine clearance > 50 mL/min Bilirubin ≤ 1.5 mg/dL
- •Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- •Aspartate transaminase (AST) ≤ 2.5 x ULN
- •Prothrombin time (PT) ≤ 1.5 x ULN
- •International Normalized Ratio (INR) ≤ 1.5 x ULN
- •Partial thromboplastin time (PTT) ≤ 1.5 x ULN
- •Subjects of childbearing potential must agree to use hormonal or barrier birth control with spermicidal gel to avoid pregnancy during the study
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Has a history of spontaneous or tumor related cerebral hemorrhage; or has cerebral hemorrhage as determined by the screening FDG PET CT and MRI. This does not include stable post operative blood products seen on a gradient echo MRI sequence.
- •Has the any of the following cardiac history:
- •Active heart disease including myocardial infarction within previous 3 months
- •Symptomatic coronary artery disease
- •Arrhythmias not controlled by medication
- •Unstable angina pectoris
- •Uncontrolled or symptomatic congestive heart failure (NYHA class III and IV) 3.2.3 Uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, including any of the following, but not limited to:
- •Epistaxis
- •Hemoptysis
- •Hematochezia
- •Hematuria
- •Gastrointestinal bleeding
- •Spontaneous or tumor related intracranial hemorrhage
- •Known predisposition for bleeding such as von Willebrand's disease or other such condition(s)
- •Uncontrolled concurrent illness that would limit compliance with study requirements, including any of the following, but limited to:
- •Uncontrolled infection.
- •Psychiatric illness/social situations
- •Prior malignancy except for non melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to 1st dose of investigational drug
- •Receiving any of the following medications:
- •Therapeutic doses of any anticoagulant, including low molecular weight heparin (LMWH). Concomitant use of warfarin, even at prophylactic doses, is prohibited
- •Digoxin, digitoxin, lanatoside C, or any type of digitalis alkaloids.
- •Colony stimulating factors (CSFs) that cannot be held during the monitoring period for dose limiting toxicities (DLT)
- •Has significant toxicities from prior treatment that have not resolved or stabilized
- •Known allergy to Coenzyme Q10
- •Known allergy or adverse reaction to oral, subcutaneous, or intravenous vitamin K
- •Is pregnant or lactating
- •Known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is not required for eligibility, but if performed previously and was positive, the subject is ineligible.
研究组 & 干预措施
Treatment (BPM31510)
Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (BPM31510)
Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (BPM31510)
Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Ubidecarenone Injectable Nanosuspension (Drug)
结局指标
主要结局
Percentage of patients with dose-limiting toxicities defined as thrombocytopenia >= grade 3, hemorrhage >= grade 3, and INR elevation >= grade 2 assessed by CTCAE v4.03
时间窗: Up to 28 days
Will be tabulated at each dose, along with the result of the pooled adjacent violators algorithm as implemented in the Modified Toxicity Probability Interval (equal weights, and the weighted mean solver).
次要结局
- Incidence of adverse events graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version (v)4.03(Up to 30 days after last dose of BPM3150)
研究者
Seema Nagpal
Clinical Assistant Professor
Stanford University