A Phase 1 Ascending-dose Study to Assess the Safety and Tolerability and Imaging Potential of Hyperpolarized Pyruvate (13C) Injection in Subjects With Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
研究概览
简要总结
Current imaging options do not assess prostate cancer well. This study will combine two magnetic resonance imaging modalities, MRI and MRSI, in order to determine the utility to physicians and patients with prostate cancer in making treatment decisions and seeing how well various types of treatment work. Hyperpolarized pyruvate (13C) is an investigational product that may enhance the imaging capability of MRI and MRSI. Hyperpolarized pyruvate will be injected into the body to determine how it is metabolized and how it's metabolism can be assessed using MR imaging.
The purpose of this study is to determine the safety and metabolism of hyperpolarized pyruvate in humans, and how this can be used to increase the effectiveness of MR imaging with regards to patient care.
详细描述
This is a phase 1 clinical study of an investigational medicinal product (IMP), hyperpolarized Pyruvate (13C) Injection. The study includes the acquisition of magnetic resonance (MR) data and will be performed in men with prostate cancer and intact prostates.
A standard dose-escalation design will be used; initially, 6 subjects will receive IMP at each dose level. As data on both the dynamics of arrival of the IMP and potential imaging efficacy are needed at each dose level, requiring the use of separate MR acquisition sequences, a modified 3+3 design will be applied in each dose cohort. The first 3 subjects will undergo dynamic 13C imaging to define the kinetics of delivery and metabolism of IMP, and the second 3 subjects will undergo 13C MR spectroscopic imaging (MRSI) to obtain 3-dimensional (3-D) spatial information about metabolism of IMP in regions of the prostate with and without cancer involvement.
After the apparent maximum tolerated dose (MTD) has been established, there will be an expansion of the 3-D imaging cohort to 6 subjects (9 subjects in total at this dose level) to obtain additional information regarding safety at the MTD. If >2 subjects from this cohort of 9 subjects experience a dose-limiting toxicity (DLT), the next lower dose will be defined as the MTD. At the dose level with the highest contrast to noise ratio (dose level less than or equal to the MTD) there will be an expansion of the imaging cohort to include another 15 subjects for a total of 18 subjects who undergo 13C 3-D scanning at this dose, to obtain exploratory information concerning the time course and SNR (signal to noise ratio) of the presence of hyperpolarized [1 13C] pyruvate and its metabolites in regions of cancer and benign prostate tissues. The information provided by these data will be used to develop the MR imaging protocol for future clinical trials that will seek to address the sensitivity and specificity of the technology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1
0.14 ml/kg bw - hyperpolarized pyruvate
干预措施: Hyperpolarized Pyruvate (13C) injection (Drug)
2
0.28 ml/kg bw - hyperpolarized pyruvate
干预措施: Hyperpolarized Pyruvate (13C) injection (Drug)
3
0.43 ml/kg bw - hyperpolarized pyruvate
干预措施: Hyperpolarized Pyruvate (13C) injection (Drug)
结局指标
主要结局
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
时间窗: 7 days
Assessment of the occurrence of clinically significant changes in safety variables from baseline. Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Monitoring will occur to evaluate for dose-limiting toxicity. Dose-Limiting Toxicity (DLT) is defined as any toxicity greater than or equal to grade 2, 3 or 4, attributable to the imaging agent and occurring within 7 days after administration. The maximum tolerated dose will be the dose level at which \<33% DLT occurs.
次要结局
- to determine the time course and imaging window that provides the best signal-to-noise ratio (SNR) of the presence of hyperpolarized pyruvate (13C).
- To determine the kinetics and prostate metabolism of hyperpolarized pyruvate (13C)
研究者
Charles Ryan
Clinical Professor of Medicine and Urology
University of California, San Francisco