A Phase I/II Study Of A Recombinant Chimeric Protein Composed Of Transforming Growth Factor (TGF)-a And A Mutated Pseudomonas Exotoxin Termed PE38 (TP-38) In Pediatric Patients With Recurrent Or Progressive Supratentorial High Grade Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 16
- 主要终点
- Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
研究概览
简要总结
RATIONALE: The TP-38 toxin can locate tumor cells and kill them without harming normal cells. Giving TP-38 toxin directly into the tumor may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of TP-38 toxin administered directly into the brain and to see how well it works in treating young patients with recurrent or progressive supratentorial high-grade glioma.
详细描述
OBJECTIVES:
Primary
-
Phase I
-
Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma.
-
Describe the toxic effects of this drug in these patients.
-
Phase II
-
Estimate the efficacy of this drug, in terms of post-infusion survival, in these patients.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed supratentorial malignant glioma
- •Recurrent or progressive disease
- •Amenable to gross total resection, clinically indicated partial resection, or biopsy
- •Tumor must have a single solid portion at least 1 cm and no greater than 5 cm in maximum diameter
- •No tumor crossing midline
- •Tumors invading the corpus callosum that do not extend beyond to midline or into the contralateral hemisphere allowed
- •No more than 1 focus of tumor
- •No tumors involving the brainstem or cerebellum
- •No tumor dissemination (i.e., subependymal or leptomeningeal)
- •Must be on steroids ≥ 3 days prior to surgery
- •Must have received prior external beam radiotherapy (tumor dose at least 45 Gy) and completed therapy at least 8 weeks before study entry
- •No impending herniation, including midline shift greater than 0.5 cm
- •No requirement for immediate palliative treatment
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 60-100% (patients over 16 years of age) OR
- •Lansky 60-100% (patients age 16 and under)
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3*
- •Hemoglobin at least 9 g/dL* NOTE: *Transfusion independent
- •ALT and AST less than 2.5 times upper limit of normal (ULN)
- •PT and PTT no greater than ULN
- •Creatinine less than 1.5 times normal OR
- •Glomerular filtration rate greater than 70 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for at least 30 days after study participation
- •No uncontrolled seizures
- •No active infection requiring treatment
- •No unexplained febrile illness
- •No known or suspected allergies to local anesthetics
- •No systemic disease or other condition that may be associated with unacceptable anesthetic/operative risk and/or that would preclude study completion
- •No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •At least 8 weeks since prior hematopoietic stem cell transplantation
- •Chemotherapy
- •At least 6 months since prior polifeprosan 20 with carmustine implant (Gliadel® wafer)
- •At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas and 2 weeks for vincristine)
- •At least 2 weeks since prior non-cytotoxic chemotherapy
- •No other prior intracerebral chemotherapy
- •No concurrent chemotherapy
- •Endocrine therapy
- •Concurrent steroids allowed
- •Radiotherapy
- •See Disease Characteristics
- 另有 8 项未显示
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated infusion concentration of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
Toxicities of TP-38
Post-infusion survival (phase II)
Maximum safe volume rate of TP-38 infused through three catheters (Stratum A) or through two catheters (Stratum B).
次要结局
- EGFR expression and phosphorylation (activity)
- Correlation of EGFR expression with tumor histology, tumor grade, tumor response (phase I and phase II) and survival and progression-free survival (phase II).
- Post-infusion progression-free survival (phase II)
- Objective response (phase II)