A Phase I/II Study to Evaluate the Safety and Tolerance of Escalating Doses of RSR13 Administered With a Fixed Dose of BCNU Every Six Weeks in Patients With Recurrent Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 18
- 主要终点
- Safety and tolerability
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of efaproxiral when given with carmustine and to see how well they work in treating patients with progressive or recurrent malignant glioma.
详细描述
OBJECTIVES:
- Evaluate the safety and tolerability of escalating doses of efaproxiral (RSR13) when administered concurrently with carmustine in patients with progressive or recurrent malignant glioma.
- Determine the maximum tolerated dose (MTD) of RSR13 when administered with carmustine in this patient population.
- Determine the pharmacokinetic profile of this regimen in these patients.
- Estimate the efficacy of this regimen at the MTD in these patients.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of efaproxiral (RSR13).
Patients receive RSR13 IV over 30 minutes followed 30 minutes later by carmustine IV over 1-2 hours on day 1. Treatment repeats every 6 weeks for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.
Cohorts of 6-12 patients receive escalating doses of RSR13 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 5 of 12 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with RSR13 and carmustine at the recommended phase II dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 that is progressive or recurrent after radiotherapy with or without chemotherapy
- •Anaplastic astrocytoma
- •Anaplastic oligodendroglioma
- •Glioblastoma multiforme
- •Prior low-grade glioma allowed provided progression has occurred after radiotherapy with or without chemotherapy and then high-grade glioma is found on biopsy
- •Measurable disease by serial MRI or CT scan
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 60-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •Absolute neutrophil count at least 1,500/mm^3
- •Hemoglobin at least 10 g/dL
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 2.0 mg/dL
- •Alkaline phosphatase no greater than 3 times upper limit of normal (ULN)
- •SGOT and SGPT no greater than 3 times ULN
- •Creatinine no greater than 2.0 mg/dL
- •Resting oxygen saturation on room air at least 90% by pulse oximetry
- •FVC, DLCO, and FEV_1 at least 50% of normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No other serious concurrent medical illness that would preclude study compliance
- •No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 3 weeks since prior investigational biologics
- •Chemotherapy:
- •See Disease Characteristics
- •No prior nitrosoureas for glioma
- •No more than 1 prior chemotherapy regimen
- •At least 4 weeks since prior chemotherapy
- •No prior efaproxiral
- •Endocrine therapy:
- •Concurrent corticosteroids (e.g., dexamethasone) allowed
- •Radiotherapy:
- •See Disease Characteristics
- •At least 90 days since prior radiotherapy
- •Not specified
- •At least 3 weeks since other prior investigational drugs or devices
排除标准
- 未提供
结局指标
主要结局
Safety and tolerability
Maximum tolerated dose
Pharmacokinetic profile
Efficacy
次要结局
未报告次要终点