A Phase I/II, Open-Label, Non-Randomized, Multicenter, Single Agent Study Of Intravenous SDX-102 For The Treatment Of Patients With MTAP-Deficient High Grade Recurrent Malignant Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 5
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as alanosine, use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of alanosine in treating patients with high-grade progressive or recurrent malignant gliomas.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of alanosine (SDX-102) with or without enzyme-inducible antiepileptic drugs (EIAEDs) in patients with methylthioadenosine phosphorylase (MTAP)-deficient high-grade progressive or recurrent malignant gliomas.
- Determine the pharmacokinetics of this drug administered concurrently with EIAEDs in these patients.
OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study. Patients are stratified according to concurrent anticonvulsant drug use (drugs that induce hepatic metabolic enzymes vs drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drug).
Patients receive alanosine (SDX-102) IV continuously for 5 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SDX-102 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed malignant glioma of 1 of the following types:
- •Anaplastic astrocytoma
- •Anaplastic oligodendroglioma
- •Glioblastoma multiforme
- •Progressive or recurrent disease after prior radiotherapy with or without chemotherapy
- •Low-grade glioma that progressed after prior radiotherapy with or without chemotherapy and is found to be high-grade glioma after biopsy allowed
- •No more than 2 prior treatment regimens
- •Measurable disease by CT scan or MRI
- •Documented absence of methylthioadenosine phosphorylase (MTAP) on fixed tumor specimens
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Karnofsky 60-100%
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 1.5 mg/dL
- •Transaminases ≤ 4 times upper limit of normal
- •Creatinine ≤ 1.5 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception before, during, and for 4 weeks after study participation
- •Mini mental state exam score of ≥ 15
- •No psychological or sociological condition, addictive disorder, or family problem that would preclude study compliance
- •No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
- •No concurrent serious infection or medical illness that would preclude study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
- •Chemotherapy
- •See Disease Characteristics
- •At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- •Endocrine therapy
- •Must be maintained on a stable or lower corticosteroid regimen from the time of the baseline scan until the start of study treatment
- •No concurrent steroids as antiemetics
- •Radiotherapy
- •See Disease Characteristics
- •At least 3 months since prior radiotherapy
- •Not specified
- •Recovered from prior therapy
- •More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes
- •No other concurrent investigational agents
排除标准
- 未提供