A Phase II Evaluation With Correlative Studies Of Fenretinide (NSC 374551-4HPR) As A Single Agent In The Treatment Of Adult Patients With Recurrent Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This randomized phase II trial is studying how well neoadjuvant and adjuvant fenretinide works compared to adjuvant fenretinide alone in treating patients who are undergoing surgical resection for recurrent glioblastoma multiforme. Chemotherapy drugs, such as fenretinide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether neoadjuvant and adjuvant fenretinide is more effective than adjuvant fenretinide alone
详细描述
PRIMARY OBJECTIVES:
I. Compare the efficacy of neoadjuvant and adjuvant fenretinide vs adjuvant fenretinide alone, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme undergoing surgical resection II. Correlate the serum and glioma tissue pharmacology of this drug with clinical response in patients treated with these regimens.
III. Determine whether this drug induces apoptosis in glioma tissue in patients treated with these regimens.
IV. Correlate the apoptotic index with tissue and serum concentration and clinical response in patients treated with these regimens.
V. Compare radiological response, overall survival, and unexpected toxicity in patients treated with these regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Histologically confirmed glioblastoma multiforme after initial tumor resection
- •Radiologically evident recurrent tumor after prior radiotherapy OR after treatment for no more than 2 prior relapses
- •Enhancing or nonenhancing recurrent disease by MRI
- •No progressive symptoms requiring urgent surgery
- •Performance status - Karnofsky 70-100%
- •More than 8 weeks
- •Absolute granulocyte count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •PT/PTT no greater than upper limit of normal
- •SGPT no greater than 2.5 times normal
- •Alkaline phosphatase no greater than 2.5 times normal
- •Bilirubin less than 1.5 mg/dL
- •BUN no greater than 1.5 times normal
- •Creatinine no greater than 1.5 times normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 2 months after study participation
- •Amylase and lipase normal
- •No active infection
- •No other disease that would obscure toxicity or dangerously alter drug metabolism
- •No other concurrent serious medical illness
- •Not at risk from any study treatment delays
- •Able to swallow fenretinide capsules
- •Recovered from all prior chemotherapy
- •Approximately 2 weeks since prior vincristine
- •Approximately 6 weeks since prior nitrosoureas
- •Approximately 3 weeks since prior procarbazine
- •See Disease Characteristics
- •At least 2 weeks since prior radiotherapy
- •See Disease Characteristics
- •At least 1 week since prior vitamin A
- •At least 1 week since prior isotretinoin (Accutane®)
- •No concurrent vitamin A during and for 2 weeks after study participation
- •No concurrent antioxidants (e.g., ascorbic acid or vitamin E)
排除标准
- 未提供
研究组 & 干预措施
Arm I (fenretinide, surgery)
Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
干预措施: fenretinide (Drug)
Arm I (fenretinide, surgery)
Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
干预措施: therapeutic conventional surgery (Procedure)
Arm I (fenretinide, surgery)
Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
干预措施: pharmacological study (Other)
Arm I (fenretinide, surgery)
Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
干预措施: laboratory biomarker analysis (Other)
Arm II (surgery)
Patients undergo surgical resection.
干预措施: therapeutic conventional surgery (Procedure)
Arm II (surgery)
Patients undergo surgical resection.
干预措施: pharmacological study (Other)
Arm II (surgery)
Patients undergo surgical resection.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Up to 6 months
Plasma and tissue concentrations of fenretinide and its metabolite, 4-MPR using high-performance liquid chromatography (HPLC) assay
时间窗: At baseline, and at 1, 7, 14, and 21 days
Tumor apoptotic index after fenretinide treatment by immunohistochemistry
时间窗: At the time of surgery
Correlation between tumor apoptotic index with serum and tissue fenretinide levels
时间窗: At the time of surgery
Correlation of time to progression with drug levels and apoptotic index
时间窗: Up to 2 years
次要结局
- Fenretinide effects on retinol, RBP, retinoid receptor levels and IGF-1(Up to 21 days (course 1 and 4))
- Fenretinide activity using magnetic resonance spectroscopy (MRS)(At the time of surgery)
- Radiological response(Up to 2 years)
- Overall survival(Up to 2 years)
- Unexpected toxicity associated with fenretinide as assessed by CTC version 3.0(Up to 2 years)