Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) as a Diagnostic and Response Monitoring Imaging Tool in Advanced Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- Pyruvate to lactate (kPL) metabolic flux within target lesion (Cohort A)
研究概览
简要总结
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging as a diagnostic and response monitoring tool in patients with advanced prostate cancer. Preliminary pre-clinical and clinical data demonstrates the ability of HP C-13 pyruvate/metabolic MR imaging to detect high-grade prostate cancer, including cancer with neuroendocrine differentiation, as well as provide early evidence of metabolic response and resistance following application of systemic therapies for the treatment of advanced prostate cancer patients. In the proposed study, the investigators aim is to extend the initial clinical results and further develop HP C-13 MRI as an imaging modality in advanced prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine the kPL (metabolic flux from hyperpolarized [HP] [1-13C]pyruvate to [1-13C]lactate) and kPG (metabolic flux from HP [2-13C]pyruvate to [5-13C]glutamate) within target lesion. (Cohort A) II. To determine the mean percent change from baseline in intra-tumoral kPL and kPG within target lesion. (Cohort B)
SECONDARY OBJECTIVE:
I. To descriptively report on the intra-tumor heterogeneity in kPL and kPG measurement within target lesion. (Cohorts A and B)
EXPLORATORY (CORRELATIVE) OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Histologically-confirmed locally advanced or metastatic prostate cancer. Patients with unequivocal clinical evidence supporting diagnosis of prostate cancer who have not had prior biopsy may be considered eligible per judgment of Principal Investigator.
- •Presence of at least one target lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:
- •Soft tissue/visceral organ target lesions must measure at 1 cm in long axis diameter on CT or MRI.
- •Target lesions in the bone must be visualized by CT or MRI (lesions present only on bone scan do not qualify).
- •For patients with target lesion in prostate/prostatic bed:
- •i. No contra-indications to endorectal coil insertion (e.g., patients with a prior abdominoperineal resection of the rectum or latex allergy).
- •ii. No prior local treatment to the selected lesion, or evidence of radiographic progression following prior local therapy to selected lesion.
- •Able and willing to comply with study procedures and provide signed and dated informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •For patients undergoing optional tumor biopsy:
- •No history of bleeding diathesis.
- •Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy.
排除标准
- •Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- •Patients unwilling or unable to undergo MR imaging, including patients with contra- indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- •Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MRI.
- •Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures
研究组 & 干预措施
Cohort B: Hyperpolarized C13 MRI at multiple time points
Participants will undergo hyperpolarized (HP) C13 MRI at baseline and 12 weeks (+/- 8 weeks). Participants in Cohort B may undergo additional optional MR imaging at the time of disease progression. the same sequence of injections (C-1 labeled pyruvate first, C-2 labeled pyruvate second) will be used for subsequent scan time points as well.
干预措施: Hyperpolarized C13 (Drug)
Cohort B: Hyperpolarized C13 MRI at multiple time points
Participants will undergo hyperpolarized (HP) C13 MRI at baseline and 12 weeks (+/- 8 weeks). Participants in Cohort B may undergo additional optional MR imaging at the time of disease progression. the same sequence of injections (C-1 labeled pyruvate first, C-2 labeled pyruvate second) will be used for subsequent scan time points as well.
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
Cohort A: Hyperpolarized C13 MRI at a single time point
Participants will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at a single time point and will receive up to two 13C pyruvate (C-1 and C-2 labeled 13C pyruvate) investigational medicinal product (IMP) injections on the day of imaging (2nd injection is optional), as well as optional MR- or CT- guided tumor biopsies at baseline and at the time of disease progression following completion of HP C-13 MRI at the corresponding time point
干预措施: Hyperpolarized C13 (Drug)
Cohort A: Hyperpolarized C13 MRI at a single time point
Participants will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at a single time point and will receive up to two 13C pyruvate (C-1 and C-2 labeled 13C pyruvate) investigational medicinal product (IMP) injections on the day of imaging (2nd injection is optional), as well as optional MR- or CT- guided tumor biopsies at baseline and at the time of disease progression following completion of HP C-13 MRI at the corresponding time point
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
结局指标
主要结局
Pyruvate to lactate (kPL) metabolic flux within target lesion (Cohort A)
时间窗: 1 day
The metabolic flux of kPL within the target lesion will be determined for each participant enrolled in Cohort A. Descriptive statistics will be used to summarize the kPL measurements with the mean, standard deviation, and 95% confidence interval
Pyruvate to glutamate (kPG) metabolic flux within target lesion (Cohort A).
时间窗: 1 day
The metabolic flux of kPG within the target lesion will be determined for each participant enrolled in Cohort A. Descriptive statistics will be used to summarize the kPG measurements with the mean, standard deviation, and 95% confidence interval
Mean percent change from baseline in intra-tumoral kPL within target lesion after treatment. (Cohort B)
时间窗: Up to 8 weeks
The mean percent change from baseline in intra-tumoral kPL to repeat metabolic MRI obtained at the time of radiographic disease progression by PCWG3 criteria will be descriptively reported for the entire study cohort and for the subgroups of participants with treatment- refractory and treatment-responsive prostate cancer. A paired t-test or signed rank Wilcoxon test will be used to compare follow up versus baseline kPL in target lesion in participants enrolled in Cohort B.
Mean percent change from baseline in intra-tumoral kPG within target lesion after treatment.
时间窗: Up to 8 weeks
The mean percent change from baseline in intra-tumoral kPG to repeat metabolic MRI obtained at the time of radiographic disease progression by PCWG3 criteria will be descriptively reported for the entire study cohort and for the subgroups of participants with treatment- refractory and treatment-responsive prostate cancer. A paired t-test or signed rank Wilcoxon test will be used to compare follow up versus baseline kPG in target lesion in participants enrolled in Cohort B.
次要结局
- Intra-tumoral range of kPG measurement within target lesion(Up to 1 year)
- Intra-tumoral range of kPL measurement within target lesion(Up to 1 year)
研究者
Ivan de Kouchkovsky, MD
Principal Investigator
University of California, San Francisco