Melphalan With BBBD in Treating Patients With Brain Malignancies
Intra-Arterial Melphalan (L-Phenylalanine Mustard) Administered in Conjunction With Osmotic Blood-Brain Barrier Disruption in Patients With Brain Malignancies: A Phase I Study
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving drugs directly into the arteries around the tumor may kill more tumor cells. Mannitol may open the blood vessels around the brain [Blood-Brain Barrier Disruption (BBBD)]and allow melphalan to be carried directly to the brain tumor. Giving melphalan together with BBBD may be an effective treatment for central nervous system cancer.
PURPOSE: This phase I trial is studying side effects and best dose of melphalan when given together with mannitol in treating patients with central nervous system cancer.
研究概览
详细说明
OBJECTIVES:
- Determine the maximum tolerated dose of intra-arterial melphalan when given in combination with BBBD in patients with primary or metastatic central nervous system (CNS) malignancy.
- Determine the toxic effects of melphalan given with BBBD in these patients.
- Determine, preliminarily, the efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation study of melphalan.
Patients receive intra-arterial mannitol with BBBD followed by intra-arterial melphalan over 10 minutes on days 1 and 2*. Treatment repeats every 4 weeks for up to 12 monthly courses in the absence of disease progression or unacceptable toxicity .
NOTE: *Patients with gliomas localized to the posterior circulation (i.e., brain stem gliomas) receive melphalan on day 1 only.
Cohorts of 3-6 patients receive escalating doses of melphalan 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.
After completion of study therapy, patients are followed every 3 months for 1 year; every 6 months for the next 2 years; then annually.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Oregon
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Portland、Oregon、美国、97239-3098
- Knight Cancer Institute At Oregon Health and Science University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
INCLUSION CRITERIA:
- Signed written informed consent form in accordance with institutional guidelines
- Histologically confirmed primary or metastatic CNS malignancy (Patients with metastatic disease must have histological confirmation of the primary cancer AND confirmation by surgical specimen, cerebrospinal fluid cytology, elevated tumor markers, or clinical evidence of CNS involvement)
- Single or multiple cerebellar or cerebral cortex lesions allowed
- Life expectancy at least 60 days
- Radiographically evaluable disease by MRI or CT scan
- Age 18 years or older
- At least 28 days since prior radiotherapy (systemic, cranial, and/or spinal)
- At least 28 days since prior chemotherapy (42 days for nitrosoureas)
- Adequate cardiac and pulmonary function to tolerate general anesthesia
- Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2
- Other tumor masses in the spinal cord allowed provided there is no radiographic or clinical evidence of spinal cord block
- Available for follow-up for at least one year following completion of treatment
- Fertile patients must use effective contraception for 2 months prior to, during, and for 3 months after study participation
Pre-treatment lab tests within 14 days prior to initiation of treatment:
- White blood cell count (WBC) > 2,500/mm^3
- Absolute granulocyte count > 1,200/mm^3
- Platelet count > 100,000/mm^3
- Hematocrit > 30% (transfusion allowed)
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times ULN
- Creatinine ≤ 2 times ULN
- Subjects with history of smoking or emphysema require diffusing capacity of lung for carbon monoxide (DLCO) ≥ 80% of predicted value for age
- Histological sections submitted for pathology review
EXCLUSION CRITERIA:
- Radiographic evidence of excessive intra-cranial mass effect and/or spinal block
- Known hypersensitivity or intolerance to melphalan
- NCI CTC Grade 3 or greater baseline neurologic symptoms
- Immunologically compromised (Concurrent corticosteroids for tumor edema allowed)
- Unable to tolerate general anesthesia
- Pregnant, positive human chorionic gonadotropin (HCG) test, or lactating
- HIV positive
- Receiving concurrent radiotherapy or immunotherapy
- Serious illness that would preclude study participation
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：所有科目
|
All levels: Every 4 weeks for up to one year Dose Escalation Plan: Level 1: 4mg/m2/day x 2 days Level 2: 6mg/m2/day x 2 days Level 3: 8mg/m2/day x 2 days Level 4: 10mg/m2/day x 2 days Level 5: 12mg/m2/day x 2 days |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Maximum tolerated dose (MTD)of Melphalan as measured by NCI common toxicity criteria (CTC) v2 toxicities
大体时间：5 years
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MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects
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5 years
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
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Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment
大体时间：5 years
|
5 years
|
合作者和调查者
调查人员
- 首席研究员：Edward A. Neuwelt, MD、OHSU Knight Cancer Institute
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- IRB00001299
- P30CA069533 (美国 NIH 拨款/合同)
- 1299 (OHSU eIRB)
- 4834 (其他标识符：OHSU IRB (discontinued number))
- ONC-98018-L (其他标识符：OHSU Knight Cancer Institute)
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