A Multi-center, Open-label, Randomized, Controlled Phase I Trial to Investigate the Effects of Cilengitide (EMD 121974) Using Dynamic MR and FET-PET Imaging as a Pharmacodynamic Measure of Response in Subjects With Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Rate constant for passive contrast agent plasma/interstitium transfer (ktrans)
研究概览
简要总结
The main purpose of this clinical trial is to find out if cilengitide has an effect on brain tumor cells but also particularly on the blood vessels supplying the tumor with nutrient and oxygen in patients newly diagnosed with non-resectable (inoperable) glioblastoma.
In addition, this clinical trial will investigate if the addition of cilengitide in combination with standard treatment prolongs life in patients with non-resectable glioblastoma. Similarly, the duration of response of the cancer to this treatment and the side effects of the therapy will be analyzed. Furthermore, additional data on how the body deals with this substance will be collected (this is called pharmacokinetics or pharmacokinetic (PK) analysis). In this clinical trial the investigators would also like to learn more about the disease and the response to the experimental medication by measuring certain "markers".
This imaging trial will investigate the biological effects of cilengitide monotherapy on the tumor microvascular function and tumor viability in a homogenous non-pretreated subject population with newly diagnosed Gliobastoma (GBM). The purpose of this clinical trial is to study the effect that cilengitide may have on certain markers of cancer in your tumor and/or blood and to learn if there are any disease-related markers that could help in predicting how subjects respond to the administration of cilengitide.
The investigators anticipate that approximately 30 subjects will participate in this clinical trial. The clinical trial will be conducted in approximately 4 medical centers in the following countries: Germany, Poland, and Switzerland. The investigators anticipate the clinical trial will last until the end of 2013. Your participation in the trial may last up to 86 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subject aged ≥ 18 to ≤ 70 years at the time of informed consent signature
- •Tumor tissue specimens taken from multimodal imaging-guided stereotactic biopsy must be available for histopathological confirmation of GBM and potential subsequent analysis of tissue molecular markers
- •Newly diagnosed histologically proven supratentorial GBM (World Health Organization [WHO] Grade IV)
- •Subject with non-resectable GBM
- •Available dynamic MRI and FET-PET scan prior to randomization
- •Available Gd-MRI performed prior randomization
- •ECOG Performance status of 0-2
- •Stable or decreasing dose of steroids for >= 5 days prior to randomization
- •Given written informed consent
排除标准
- •Prior chemotherapy within the last 5 years
- •Prior RTX of the head (except for low-dose radiotherapy for Tinea capitis)
- •Gross total resection/partial resection (GBM surgery), placement of Gliadel® wafer
- •Receiving concurrent investigational agents or receipt of an investigational agent within the past 30 days prior to the first day of intensified imaging (W1D1)
- •Prior systemic antiangiogenic therapy
- •Inability to undergo dynamic MR or FET-PET imaging
- •History of allergic reactions attributed to Gadolinium-based contrast agents for MRI, compounds of similar chemical or biological composition
- •Planned major surgery for other diseases
- •History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months prior to enrollment
- •History of other malignant disease or acute malignant disease. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥ 5 years are eligible for this study
- •Current or history of bleeding disorders and/or history of thromboembolic events
- •Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months prior to enrollment, uncontrolled arterial hypertension
研究组 & 干预措施
Group A = Cilengitide Group
Cilengitide + SoC (Temolozomide + Radiotherapy)
干预措施: Drug (including placebo) (Drug)
Group B = Control Group
SoC (Temolozomide + Radiotherapy)
干预措施: Standard therapy (Other)
结局指标
主要结局
Rate constant for passive contrast agent plasma/interstitium transfer (ktrans)
时间窗: 2 weeks
Any change in tumor kinetic model parameter (maximum increase in ktrans) to assess the tumor microvasculature structure and function
Fractional blood plasma volume (vp)
时间窗: 2 weeks
Any change in tumor kinetic model parameter (maximum change in vp) to assess the tumor microvasculature structure and function
Maximum tumor to brain ratio (TBRmax)
时间窗: 2 weeks
Assessment of tumor amino acid (FET) uptake (tumor viability)
次要结局
- Total tumor volume and enhancing tumor volume(2 weeks)
- Interstitial space volume fraction (putative contrast agent distribution volume) (=ve)(2 weeks)
- Apparent Diffusion coefficient (ADC)(2 weeks)
- Fractional anisotropy (FA)(2 weeks)
- Kinetic behavior of [18F]FET uptake(2 weeks)
- Mean spin-lattice relaxation time of unbound protons in water(2 weeks)