前列腺癌患者使用超极化 13C-丙酮酸盐 +/- 13C,15N-尿素进行磁共振 (MR) 成像
接受放射治疗的前列腺癌患者使用超极化 13C-丙酮酸盐 +/- 13C,15N-尿素进行磁共振 (MR) 成像的 2 期研究
This is a Phase 2 clinical study of hyperpolarized (HP) 13C-pyruvate (13C), 15N-urea (13C,15N) metabolic MR imaging in prostate cancer patients who are undergoing or have received radiation therapy for prostate cancer.
研究概览
地位
条件
详细说明
PRIMARY OBJECTIVES:
I. Part 1: To Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral kPL and kPG in regions of tumor vs. adjacent benign tissue as assessed by mpMRI imaging characteristics.
II. Part 2A To perform HP 13C-MRI and measure the changes in tumoral kPL and kPG.
III. Part 2B: To perform HP 13C-MRI and study the metabolic effects (changes in tumor kPL and kPG).
IV. Part 3: To perform HP 13C-MRI at time of Biochemical Failure and measure tumoral kPL and kPG, in previously external beam radiation therapy (EBRT) treated patients.
SECONDARY OBJECTIVES:
I. To evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies (Part 1, 2 & 3).
II. To determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. (Part 2 & 3).
III. To determine the association between changes in intra-tumor kPL after 4-12 weeks of systemic hormone therapy and PSA response (Part 2B).
IV. To compare and contrast intra-tumoral kPL and kPG with Prostate Imaging Reporting and Data System (PI-RADS) version 2 and individual mpMRI parameters including apparent diffusion coefficient (ADC) on diffusion-weighted imaging (Part 1, 2 & 3).
V. To describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP-MRI exam. (Part 3).
VI. To further characterize the safety profile of HP C-13 pyruvate injections (Part 1, 2 & 3).
VII. For patients imaged with HP 13C-MRI at time of biochemical failure post-EBRT, correlate peak intra-tumoral kPL and kPG with radiotherapy dose distributions from EBRT course (Part 3).
VIII. For studies incorporating HP 13C-urea, the baseline and the on-treatment changes in urea AUC parameter will be measured and compared to kPL endpoints of the same lesions (Part 1, 2 & 3).
OUTLINE:
The study is divided into 3 parts. Part 1: Participants undergo imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam to determine exact parameters for imaging.
Part 2A: Participants planned for external beam radiotherapy (EBRT) Part 2B: Participants with high-risk localized prostate cancer planned to receive primary radiation therapy with concurrent systemic hormone therapy Part 3: Evaluable EBRT participants scanned at time of biochemical failure and MR/US fusion-guided prostate biopsy within 12 weeks. Participants have the option of undergoing a follow up HP Pyruvate +/- Urea MR exam 6-15 months following the baseline scan.
All participants will receive a scan at baseline and other procedures may be performed as part of routine, non-interventional standard of care at the time of biochemical failure, including serial prostate-specific antigen (PSA) monitoring and gene expression profiling of tumor tissue. Participants will be followed for 24 months after last procedure or removal from study, or until death, whichever occurs first.
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习地点
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California
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San Francisco、California、美国、94143
- University of California, San Francisco
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
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Participants must have biopsy-proven adenocarcinoma of the prostate, as determined by medical chart review.
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For:
- Part 1: Participants post-radiation therapy or currently considering EBRT.
- Part 2A: Participants currently scheduled for or considering EBRT (no neo-adjuvant therapy planned).
- Part 2B: Participants currently scheduled for or considering EBRT and neo-adjuvant therapy is planned. The participant has biopsy-proven adenocarcinoma of the prostate with high-risk disease, defined by the presence of at least two of following criteria: a tumor stage of T3 or T4, a Gleason score of 8 to 10, or a PSA level ≥40 ng/mL) and the participant must be planning to receive androgen deprivation therapy (ADT) with an Luteinizing hormone-releasing hormone (LHRH) agonist or antagonist. The addition of an androgen-receptor (AR) signaling inhibitor (e.g., abiraterone, bicalutamide,apalutamide, enzalutamide or darolutamide) will be allowed.
- Part 3: Participants who have previously received radiation treatment to the prostate and are exhibiting signs of biochemical failure, with planned fusion biopsy within 12 weeks following completion of baseline HP 13C pyruvate +/-urea mpMRI.
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Participant is able and willing to comply with study procedures and provide signed and dated informed consent.
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Eastern Cooperative Oncology Group (ECOG) performance status <= 1.
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Age >= 18 years old at time of study entry.
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Ability to understand and the willingness to sign a written informed consent document.
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Demonstrates adequate organ function as defined below:
- White Blood Cell count (WBC) >=4000 cells/μL.
- Hemoglobin ≥9.0 gm/dL.
- Platelets ≥75,000 cells/μL.
- Renal Function > 30 Epithelial Growth Factor Receptor (eGFR).
Exclusion Criteria:
- Evidence of pelvic regional or distant metastatic disease on conventional imaging (MRI, computed tomography or whole body bone scan) or prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET) imaging. PSMA-avid lymph nodes confined to the pelvis will be allowed if <1 centimeter (cm).
- Prostate biopsy performed within 14 days prior to baseline C-13 HP pyruvate MRI.
- Poorly controlled hypertension, with blood pressure at study entry > 160 mm Hg systolic or > 100 mm Hg diastolic. Treatment with anti-hypertensives and re-screening is permitted.
- Contraindication to or inability to tolerate MRI with endorectal coil (e.g. severe claustrophobia, presence of cardiac pacemaker, aneurysm clip, severe or painful hemorrhoids, rectal stricture).
- Congestive heart failure with New York Heart Association (NYHA) status >= 2.
- History of clinically significant ECG abnormality, including QT prolongation, a family history of prolonged QT interval syndrome or myocardial infarction within 6 months of study entry.
学习计划
研究是如何设计的？
设计细节
- 主要用途：诊断
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Part 1: Image Optimization Group
Participants will undergo Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea imaging as part of a multi-parametric magnetic resonance imaging (mpMRI) exam, with the primary objective of optimizing imaging sequences and techniques to maximize signal-to-noise ratio of imaging modality. |
Given IV
其他名称：
Imaging scan
其他名称：
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|
实验性的：Part 2A: Prospective imaging (External beam radiotherapy (EBRT) Participants)
Participants with pre-planned, non-interventional stereotactic body radiotherapy (EBRT) will undergo an HP Pyruvate +/-Urea mpMRI exam at baseline, at 3 months post-EBRT treatment and at 1yr post-treatment. |
Given IV
其他名称：
Imaging scan
其他名称：
External beam radiotherapy given outside of this study
其他名称：
|
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实验性的：Part 2B: Prospective imaging (High-risk localized prostate cancer)
Participants with with high-risk localized prostate cancer and have pre-planned, non-interventional primary radiation therapy (RT) with concurrent, systemic, non-interventional hormone therapy will undergo HP Pyruvate+/-Urea mpMRI at baseline prior to the start of systemic hormone therapy, 4-12 weeks after the initiation of systemic hormone therapy (prior to radiation therapy), at 3 months post-radiation therapy, and at +1yr post-radiation therapy. |
Given IV
其他名称：
Imaging scan
其他名称：
Radiation therapy given outside of this study
其他名称：
Therapy given outside of this study as part of standard of care
其他名称：
|
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实验性的：Part 3: EBRT participants at time of biochemical recurrence (BCR)
Evaluable EBRT participants who undergo HP Pyruvate +/-Urea mpMRI at time of biochemical failure, followed by magnetic resonance (MR) / ultrasound (US) fusion-guided prostate biopsy within 12 weeks following baseline MR exam. Participants in this group have the option of undergoing a follow up HP Pyruvate +/-Urea MR exam 6-15 months following the baseline scan, to evaluate for any interval change. |
Given IV
其他名称：
Imaging scan
其他名称：
External beam radiotherapy given outside of this study
其他名称：
Biopsies may be taken from Trans-rectal ultrasound (TRUS) -visible lesion at the urologist's discretion
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Signal-to-noise ratio (Part 1)
大体时间：Day of MR imaging (1 day)
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A signal-to-noise ratio is defined as a MR/spectroscopy parameter, consisting of the HP C13-Pyruvate or Lactate signal (peak) relative to background noise level (baseline) in MRI spectra of the tissue. |
Day of MR imaging (1 day)
|
|
Mean HP 13C-pyruvate to lactate metabolic rate of conversion (kPL) over time (Part 2A)
大体时间：Up to 24 months
|
The mean percent change in tumoral kPL between baseline and 1-year post-EBRT will be reported. |
Up to 24 months
|
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Mean HP 13C-pyruvate to glutamate metabolic rate of conversion (kPG) over time (Part 2A)
大体时间：Up to 24 months
|
The mean percent change in tumoral kPG between baseline and 1-year post-EBRT will be reported. |
Up to 24 months
|
|
Mean change in on-treatment kPL over time (Part 2B)
大体时间：Up to 24 months
|
Mean percent change in tumoral kPL for participants receiving systemic hormone therapy between baseline and 1 -year post-EBRT will be reported. |
Up to 24 months
|
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Mean change in on-treatment kPG over time (Part 2B)
大体时间：Up to 24 months
|
Mean percent change in tumoral kPG for participants receiving systemic hormone therapy between baseline and 1 -year post-EBRT will be reported. |
Up to 24 months
|
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Mean kPL at time of biochemical failure (Part 3)
大体时间：Up to 24 months
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The mean kPL for participants with biochemical failure will be reported. |
Up to 24 months
|
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Mean kPG at time of biochemical failure (Part 3)
大体时间：Up to 24 months
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The mean kPG for participants with biochemical failure will be reported. |
Up to 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Intra-patient variability of kPL
大体时间：Up to 12 months
|
Intra-patient variability in the kPL will be summarized by the intraclass correlation and presented with a 90% confidence interval when multiple HP-MRI scans are obtained for a participant. |
Up to 12 months
|
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Intra-patient variability of kPG
大体时间：Up to 12 months
|
Intra-patient variability in the kPG will be summarized by the intraclass correlation and presented with a 90% confidence interval when multiple HP-MRI scans are obtained for a participant. |
Up to 12 months
|
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Mean intra-tumoral kPL above and below the median PSA (Parts 2-3) and the mean serum PSA
大体时间：Up to 24 months
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The study cohort will be dichotomized by mean intra-tumoral kPL obtained at baseline with median serum PSA and will be compared between the two dichotomized subgroups using Mann-Whitney test. |
Up to 24 months
|
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Correlation of kPL with Prostate Imaging Reporting and Data System (PI-RADS) version 2 classification score
大体时间：Up to 24 months
|
Spearman's rank order correlation coefficient will be used to determine the relationship between kPL with PI-RADS version 2 classification score (1 through 5; PI-RADS 1 - Very low (clinically significant cancer is highly unlikely to be present) PI-RADS 2 - Low (clinically significant cancer is unlikely to be present)). The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association. |
Up to 24 months
|
|
Correlation of kPG with PI-RADS version 2 classification score
大体时间：Up to 24 months
|
Spearman's rank order correlation coefficient will be used to determine the relationship between kPL with PI-RADS version 2 classification score (1 through 5; PI-RADS 1 - Very low (clinically significant cancer is highly unlikely to be present) PI-RADS 2 - Low (clinically significant cancer is unlikely to be present)). The Spearman's correlation coefficient (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association. |
Up to 24 months
|
|
Proportion of participants with concordant mismatch of low HP 13C-urea perfusion (ureaAUC)
大体时间：Up to 24 months
|
A secondary endpoint will be to identify concordant mismatch of low HP 13C-urea perfusion (ureaAUC) in lesions assessed for kPL. |
Up to 24 months
|
|
Mean percent change in kPL over time for participants with optional scan
大体时间：Up to 24 months
|
For the subset of participants who undergo optional follow up MR scan following baseline MRI, the mean percent change from baseline in kPL will be descriptively reported using summary statistics. |
Up to 24 months
|
|
Number of participants with reported treatment-related adverse events
大体时间：From start of HP 13C-pyruvate MR imaging to 20 minutes after the procedure for all scans
|
The incidence of adverse events as graded by Common Toxicity Criteria version 5.0 will be determined |
From start of HP 13C-pyruvate MR imaging to 20 minutes after the procedure for all scans
|
合作者和调查者
调查人员
- 首席研究员：Robert Bok, MD, PhD、University of California, San Francisco
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- 24922
- 5R01CA238379 (美国 NIH 拨款/合同)
- NCI-2024-03775 (注册表标识符：NCI Clinical Trials Reporting Program)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
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