A Phase I Study of a Recombinant Chimeric Protein Composed of Circularly Permuted IL-4 and a Mutated Form of the Pseudomonas Exotoxin Termed IL-4(38-37)-PE38KDEL (IL-4 Toxin) for the Treatment of Recurrent Malignant Astrocytoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 19
研究概览
简要总结
RATIONALE: IL-4(38-37)-PE38KDEL immunotoxin may locate tumor cells and kill them without harming normal cells. This may be an effective treatment for recurrent malignant astrocytoma.
PURPOSE: Phase I trial to study the effectiveness of IL-4(38-37)-PE38KDEL immunotoxin in treating patients who have recurrent malignant astrocytoma.
详细描述
OBJECTIVES: I. Determine the maximum tolerated dose of intratumorally infused IL-4(38-37)-PE38KDEL immunotoxin in patients with recurrent malignant astrocytoma. II. Determine the safety of this regimen in these patients. III. Determine preliminarily any efficacy of this regimen in these patients.
OUTLINE: This is a dose escalation, multicenter study. Patients undergo a stereotactic biopsy under MR/CT guidance. Catheters are then placed into the tumor under stereotactic guidance. The catheter is filled with IL-4(38-37)-PE38KDEL immunotoxin (IL-4 toxin), with infusion beginning 24 hours after catheter insertion. The IL-4 toxin is infused over 4 days. The catheter is removed 45 minutes after the infusion is completed and a MR scan is performed. Cohorts of 3 patients each receive escalating doses of IL-4 toxin until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding the dose at which 2 of 3 patients experience dose limiting toxicity. Patients are followed every 4 weeks for 16 weeks, then every 8 weeks for up to 3 years.
PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS: Histologically proven recurrent glioblastoma or anaplastic astrocytoma Stereotactically accessible, enhancing mass no greater than 50 mL total volume by MRI No significant mass effect Recent craniotomy allowed No anaplastic oligodendroglioma No tumors of the brainstem, cerebellum, or both hemispheres No diffuse subependymal or CSF disease If on stable or increasing dose of steroid, must have evidence of increasing contrast enhancement by MRI or CT scan Prior external beam radiotherapy required
- •PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9.5 g/dL Hepatic: Bilirubin less than 2 mg/dL AST and ALT less than 2 times upper limit of normal (ULN) PT/PTT no greater than ULN Renal: Creatinine less than 2 mg/dL Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception No systemic diseases to cause unacceptable anesthetic/operative risk No active infection requiring treatment No unexplained febrile illness
- •PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent blood or platelet transfusions Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics Medically able to undergo surgery Other: No other concurrent investigational agents
排除标准
- 未提供