A Phase 1 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Glial Tumors of the Brain
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Establishment of a safe dose for oral ALA administration
研究概览
简要总结
This phase I trial is studying the side effects and best dose of aminolevulinic acid during surgery in treating patients with malignant brain tumors. Aminolevulinic acid becomes active when it is exposed to a certain kind of light and may help doctors find and remove tumor cells during surgery
详细描述
PRIMARY OBJECTIVES I. Establish a safe dose for oral ALA administration.
SECONDARY OBJECTIVES I. Determine which of 3 ALA (aminolevulinic acid) doses (10, 20 or 30 mg/kg) provide optimal discrimination between normal and malignant tissue intraoperatively.
II. Determine whether or not the use of ALA (compared to comparable cases performed without the aid of ALA) leads to a higher rate of gross total resection, as determined by postoperative MRI scanning within 48 hour of surgery completion.
III. Compare time-to-progression and survival to that in comparable cases performed without the aid of ALA.
OUTLINE: This is a phase I, dose-escalation study
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients may have clinically documented primary malignant glioma for which re-resection is clinically indicated; in this instance, previous pathology slides will be reviewed by University of Washington Medical Center (UWMC) Neuropathology prior to surgery; alternatively, patients may have imaging studies (magnetic resonance imaging [MRI] and /or computed tomography [CT] scans), which are highly indicative of a new malignant glioma, for which surgical resection is clinically warranted; the anticipated histology at resection should include: glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma (mixed glioma)
- •Prior therapy is not a consideration in protocol entry; patients with recurrence of known malignant gliomas are eligible following UWMC neuropathology slide review
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- •Life expectancy is not a consideration for protocol entry
- •Patients must have normal organ and marrow function as defined below:
- •Leukocytes >= 3,000/uL
- •Absolute neutrophil count >= 1,500/uL
- •Platelets >= 100,000/uL
- •Total bilirubin within normal institutional limits
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- •Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •The effects of ALA on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Prior therapy is not an exclusion criterion
- •Patients may not be receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ALA
- •Personal or family history of porphyrias
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because ALA is of unknown teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ALA, breastfeeding should be discontinued if the mother is treated with ALA
研究组 & 干预措施
Treatment (photodynamic therapy)
Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.
干预措施: aminolevulinic acid (Drug)
Treatment (photodynamic therapy)
Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.
干预措施: laboratory biomarker analysis (Other)
Treatment (photodynamic therapy)
Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.
干预措施: therapeutic conventional surgery (Procedure)
结局指标
主要结局
Establishment of a safe dose for oral ALA administration
时间窗: For 30 days post-aminolevulinic acid dose
Using National Cancer Institute (NCI) Common Toxicity Criteria to quantify toxicity following ALA administration. We will use descriptive statistics to analyze the safety data, based on NCI toxicity criteria.
Determination of which of 3 ALA doses provide optimal discrimination between normal and malignant tissue intraoperatively
时间窗: During surgery and from samples collected during surgery
The results from three methods will be used collectively to determine whether or not it is prudent, safe and justified to proceed with 12 more patients using the highest dose tolerated without undue toxicity. The results from these three methods, both surgical fluorescence rating and neuropathologist ratings of fluorescence and presence, or absence, of tumor will be compared using a correlation coefficient.
次要结局
- Comparison of time-to-progression (TTP) and survival to that in comparable cases performed without the aid of ALA(At week 5 and then every 8-12 weeks for 27 months)