A Phase 2 Study of Magnetic Resonance (MR) Imaging With Hyperpolarized 13C-Pyruvate +/- 13C,15N-Urea in Patients With Prostate Cancer Undergoing Radiation Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 161
- 试验地点
- 2
- 主要终点
- Signal-to-noise ratio (Part 1)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Participants must have biopsy-proven adenocarcinoma of the prostate, as determined by medical chart review.
- •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.
- •Participant is able and willing to comply with study procedures and provide signed and dated informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status <=
- •Age >= 18 years old at time of study entry.
- •Ability to understand and the willingness to sign a written informed consent document.
- •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).
排除标准
- •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 >=
- •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.
研究组 & 干预措施
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.
干预措施: hyperpolarized pyruvate +/-urea (13C/15N) (Drug)
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.
干预措施: Multi-parametric magnetic resonance imaging (mpMRI) (Procedure)
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.
干预措施: hyperpolarized pyruvate +/-urea (13C/15N) (Drug)
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.
干预措施: Non-investigational External beam radiotherapy (EBRT) (Radiation)
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.
干预措施: Multi-parametric magnetic resonance imaging (mpMRI) (Procedure)
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.
干预措施: hyperpolarized pyruvate +/-urea (13C/15N) (Drug)
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.
干预措施: Radiotherapy (RT) (Procedure)
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.
干预措施: Multi-parametric magnetic resonance imaging (mpMRI) (Procedure)
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.
干预措施: Non-interventional hormone therapy (Biological)
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.
干预措施: hyperpolarized pyruvate +/-urea (13C/15N) (Drug)
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.
干预措施: Non-investigational External beam radiotherapy (EBRT) (Radiation)
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.
干预措施: Multi-parametric magnetic resonance imaging (mpMRI) (Procedure)
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.
干预措施: Prostate Biopsy (Procedure)
结局指标
主要结局
Signal-to-noise ratio (Part 1)
时间窗: Day of MR imaging (1 day)
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.
Mean HP 13C-pyruvate to lactate metabolic rate of conversion (kPL) over time (Part 2A)
时间窗: Up to 24 months
The mean percent change in tumoral kPL between baseline and 1-year post-EBRT will be reported.
Mean HP 13C-pyruvate to glutamate metabolic rate of conversion (kPG) over time (Part 2A)
时间窗: Up to 24 months
The mean percent change in tumoral kPG between baseline and 1-year post-EBRT will be reported.
Mean change in on-treatment kPL over time (Part 2B)
时间窗: 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.
Mean change in on-treatment kPG over time (Part 2B)
时间窗: 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.
Mean kPL at time of biochemical failure (Part 3)
时间窗: Up to 24 months
The mean kPL for participants with biochemical failure will be reported.
Mean kPG at time of biochemical failure (Part 3)
时间窗: Up to 24 months
The mean kPG for participants with biochemical failure will be reported.
次要结局
- Correlation of kPG with PI-RADS version 2 classification score(Up to 24 months)
- Number of participants with reported treatment-related adverse events(From start of HP 13C-pyruvate MR imaging to 20 minutes after the procedure for all scans)
- Intra-patient variability of kPL(Up to 12 months)
- Correlation of kPL with Prostate Imaging Reporting and Data System (PI-RADS) version 2 classification score(Up to 24 months)
- Proportion of participants with concordant mismatch of low HP 13C-urea perfusion (ureaAUC)(Up to 24 months)
- Mean intra-tumoral kPL above and below the median PSA (Parts 2-3) and the mean serum PSA(Up to 24 months)
- Intra-patient variability of kPG(Up to 12 months)
- Mean percent change in kPL over time for participants with optional scan(Up to 24 months)
研究者
Robert Bok, MD, PhD
Principal Investigator
University of California, San Francisco