A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 9
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.
PURPOSE: Phase I trial to study the effectiveness of O(6)-benzylguanine given before surgery to patients who have malignant glioma.
详细描述
OBJECTIVES:
- Determine the dose of O6-benzylguanine (O6-BG) that produces total depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of patients with cerebral anaplastic astrocytoma or glioblastoma multiforme.
- Determine the qualitative and quantitative toxicities of O6-BG in this patient population.
OUTLINE: This is a dose escalation study.
Part I: The first cohort of 10 patients receives O6-benzylguanine (O6-BG) IV over 1 hour at dose level 1 beginning 6 hours prior to surgery. If at least 3 of 10 patients in the first cohort have detectable levels of O6-alkylguanine-DNA alkyltransferase (AGT), then a second cohort of 10 patients receives O6-BG as above at dose level 2. Dose escalation continues until at least 8 of 10 patients have undetectable AGT activity. At this point, 4 additional patients are accrued. If at least 11 of 14 patients at this dose level have undetectable levels of AGT, then this dose level constitutes the biologic modulatory dose of O6-BG. If less than 11 of 14 patients have undetectable levels of AGT, then 10 additional patients are treated at a higher dose. If at any time 3 or more patients at a dose level have detectable AGT activity, accrual is stopped at that dose level and patients are treated at the next higher dose level. (Part I closed to accrual effective 7/10/2000)
Part II: An additional cohort of 14 patients receives O6-BG at dose level 5 beginning 18 hours prior to surgery.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Must be undergoing a diagnostic/therapeutic craniotomy for biopsy/resection of recurrent or newly diagnosed (or presumed) cerebral anaplastic astrocytoma or glioblastoma multiforme
- •Patients undergoing stereotactic biopsy or partial resection are eligible
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •SWOG 0-2 OR
- •Karnofsky 60-100%
- •Hematopoietic:
- •WBC at least 3,500/mm3
- •Absolute neutrophil count at least 1,800/mm3
- •Platelet count at least 125,000/mm3
- •Hemoglobin at least 9 g/dL
- •Bilirubin less than 1.5 mg/dL
- •SGOT less than 2 times upper limit of normal
- •Creatinine less than 1.5 mg/dL OR
- •Creatinine clearance greater than 70 mL/min
- •Cardiovascular:
- •No cardiovascular illnesses that cannot be adequately controlled with
- •appropriate therapy or would increase risk, e.g.:
- •Severe cardiac disease such as uncontrolled arrhythmias or conduction
- •Major problems with edema (e.g., residual leg swelling from deep venous
- •thrombosis)
- •Recent coronary artery disease
- •Poorly controlled hypertension (systolic pressure greater than 180 mm Hg,
- •diastolic pressure greater than 110 mm Hg)
- •No other medical illnesses that cannot be adequately controlled with
- •appropriate therapy or would increase risk, e.g.:
- •Major problems with edema (e.g., Cushing's syndrome)
- •Major psychiatric illness
- •No other malignancy requiring active therapy
- •Not pregnant or nursing
- •Fertile patients must us effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •Must have failed or received no prior treatment with a nitrosourea,
- •procarbazine, or temozolomide
- •No prior O6-benzylguanine
- •At least 4 weeks since prior chemotherapy and recovered
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •At least 6 weeks since prior radiotherapy
- •No prior radiotherapy to greater than 10-20% of bone marrow
- •No concurrent therapy for any other malignancy
- •At least 2 weeks since other prior investigational drug
排除标准
- 未提供