A Pilot Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) to Detect High Grade Localized Prostate Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio by pathological grade (Cohort A)
研究概览
简要总结
This pilot clinical trial studies how well magnetic resonance spectroscopic imaging (MRSI) with hyperpolarized carbon 13 (13C) pyruvate alone or in combination with 13C 15N2 Urea works in finding prostate cancer that exhibits poorly differentiated or undifferentiated cells (high-grade) and that is restricted to the site of origin, without evidence of spread (localized) in patients undergoing radical prostatectomy. Diagnostic procedures, such as MRSI with hyperpolarized carbon (13C) pyruvate, may aid in the diagnosis of prostate cancer and in discriminating high-grade from low-grade prostate cancer and benign adjacent prostate tissue
详细描述
PRIMARY OBJECTIVES:
I. To investigate the association between hyperpolarized (HP) pyruvate-to-lactate conversion (kPL) and HP urea perfusion with histologic grade of prostate cancer, including benign prostate tissue, low grade disease (primary Gleason score < 4), and high grade (primary Gleason score >= 4) prostate cancer (Cohort A).
II. To investigate the association between HP pyruvate-to-lactate conversion (kPL) and HP urea perfusion with in-field clinically significant (Gleason score >3+3) recurrent/residual prostate cancer following non-investigational High-Intensity Focused Ultrasound (HIFU) focal therapy (Cohort B)
SECONDARY OBJECTIVES:
I. Safety.
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
- •Biopsy-proven adenocarcinoma of the prostate. Biopsy may be performed outside of University of California, San Francisco (UCSF), if detailed results of sextant biopsy are available. For Cohort A only, a minimum of 20 participants out of a planned enrollment of 50 patients must have high-risk disease as defined by primary Gleason score of 4 or 5 on prior prostate biopsy.
- •Cohort A only: Planned radical prostatectomy at UCSF within 12 weeks following protocol MRI/MRSI.
- •Cohort B only: HIFU focal therapy completed within 18 months of protocol MRI/MRSI, and planned systematic and MR-guided biopsy at UCSF within 12 weeks following protocol MRI/MRSI.
- •The participant is 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
排除标准
- •Participants who because of age less than 18 years old, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- •Participants unwilling or unable to undergo MR imaging, including patients with contraindications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- •Participants who cannot tolerate or have contra-indications to endorectal coil insertion; for example, participants with a prior abdominoperineal resection of the rectum or latex allergy.
- •Note: The use of an endorectal coil may be waived at the discretion of the Principal Investigator upon review of available imaging with radiology, in which case this exclusion criterion will not apply.
- •Patients with contra-indications to injection of gadolinium contrast; for example patients with prior documented allergy or those with inadequate renal function.
- •Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
- •Cryosurgery, surgery for prostate cancer, prostatic or pelvic radiotherapy prior to study enrollment. For Cohort B, HIFU focal therapy is allowed. No limit on number of prior prostate biopsies; prior transurethral prostatic resection (TURP) is not allowed.
- •Current or prior androgen deprivation therapy. For Cohort A, a history of use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least one month prior to study entry. For cohort B, a history of use of 5-α reductase inhibitor is allowed, provided it is discontinued at least 14 days to protocol MRI/MRSI.
- •Poorly controlled hypertension, with blood pressure at study entry > 160/100; the addition of anti-hypertensives to control blood pressure is allowed for eligibility determination.
- •Congestive heart failure or New York Heart Association (NYHA) status >=
- •A history of clinically significant electrocardiography (EKG) abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry; patients with rate-controlled atrial fibrillation/flutter will be allowed on study.
研究组 & 干预措施
Cohort A: Pre-surgical Prostate Cancer patients
Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed within 12 weeks of subsequent non-investigational radical prostatectomy.
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
Cohort A: Pre-surgical Prostate Cancer patients
Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed within 12 weeks of subsequent non-investigational radical prostatectomy.
干预措施: Hyperpolarized 13C,15N2-urea (Drug)
Cohort A: Pre-surgical Prostate Cancer patients
Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed within 12 weeks of subsequent non-investigational radical prostatectomy.
干预措施: Magnetic Resonance Spectroscopic Imaging (Procedure)
Cohort B: Post-HIFU Participants
Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed for participants with planned post-HIFU surveillance systematic and MR-targeted non-investigational biopsies
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
Cohort B: Post-HIFU Participants
Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed for participants with planned post-HIFU surveillance systematic and MR-targeted non-investigational biopsies
干预措施: Hyperpolarized 13C,15N2-urea (Drug)
Cohort B: Post-HIFU Participants
Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed for participants with planned post-HIFU surveillance systematic and MR-targeted non-investigational biopsies
干预措施: Magnetic Resonance Spectroscopic Imaging (Procedure)
结局指标
主要结局
Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio by pathological grade (Cohort A)
时间窗: Baseline, 1 day
Means and standard deviations for lactate area under curve will be calculated by pathologic grade (benign, low grade (primary Gleason score \<4) and high grade (primary Gleason score \>4)).
Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio (Cohort B)
时间窗: Baseline, 1 day
Means and standard deviations for lactate area under curve will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.
Mean lactate area under curve (AUC) by pathological grade (Cohort A)
时间窗: Baseline, 1 day
Means and standard deviations for lactate area under curve will be calculated by pathologic grade (benign, low grade (primary Gleason score \<4) and high grade (primary Gleason score \>4)). A One-way ANOVA model will be used to compare lactate area under curve by pathologic grade (benign, low grade (primary Gleason score \<4) and high grade (primary Gleason score \>4)).
Mean lactate area under curve (AUC) (Cohort B)
时间窗: Baseline, 1 day
Means and standard deviations for lactate area under curve will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.
Mean peak conversion of HP 13C pyruvate to lactate (kPL) by pathological grade (Cohort A)
时间窗: Baseline, 1 day
Means and standard deviations for kPL will be calculated by pathologic grade (benign, low grade (primary Gleason score \<4) and high grade (primary Gleason score \>4)).
Mean peak conversion of HP 13C pyruvate to lactate (kPL) (Cohort B)
时间窗: Baseline, 1 day
Means and standard deviations for kPL will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.
Mean Urea AUC by pathological grade (Cohort A)
时间窗: Baseline, 1 day
Means and standard deviations for Urea AUC will be calculated by pathologic grade (benign, low grade (primary Gleason score \<4) and high grade (primary Gleason score \>4)).
Mean Urea AUC (Cohort B)
时间窗: Baseline, 1 day
Means and standard deviations for Urea AUC will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.
Mean urea transfer constant (Ktrans) by pathological grade (Cohort A)
时间窗: Baseline, 1 day
Means and standard deviations for Ktrans will be calculated by pathologic grade (benign, low grade (primary Gleason score \<4) and high grade (primary Gleason score \>4)).
Mean urea transfer constant (Ktrans) (Cohort B)
时间窗: Baseline, 1 day
Means and standard deviations for Ktrans will be calculated for those with in-field recurrent/residual clinically significant prostate cancer.
次要结局
- Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort A)(Baseline, 1 day)
- Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort B)(Baseline, 1 day)
- Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort A)(Baseline, 1 day)
- Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort B)(Baseline, 1 day)
- Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort A)(Baseline, 1 day)
- Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort B)(Baseline, 1 day)
- Optimal cut-off value of urea AUC (Cohort A)(Baseline, 1 day)
- Optimal cut-off value of urea AUC (Cohort B)(Baseline, 1 day)
- Optimal cut-off value of urea transfer constant (ktrans) (Cohort A)(Baseline, 1 day)
- Optimal cut-off value of urea transfer constant (ktrans) (Cohort B)(Baseline, 1 day)
- Proportion of participants with Treatment-Related Adverse Events(Baseline, 1 day)
- Compare lactate/pyruvate area under curve (AUC) with Prostate Imaging Reporting and Data System (PI-RADS)(Baseline, 1 day)
- Compare peak lactate/pyruvate with PI-RADS(Baseline, 1 day)
- Compare pyruvate to lactate (kPL) with PI-RADS(Baseline, 1 day)
- Compare urea AUC with PI-RADS(Baseline, 1 day)
- Compare urea transfer constant (Ktrans) with PI-RADS(Baseline, 1 day)
- Mean difference in Intra-patient peak lac/pyr(Baseline, 1 day)
- Mean difference in Intra-patient lac/pyr AUC(Baseline, 1 day)
- Mean difference in Intra-patient kPL(Baseline, 1 day)
- Mean difference in Intra-patient Urea AUC(Baseline, 1 day)
- Mean difference in Intra-patient Urea ktrans(Baseline, 1 day)
研究者
Ivan de Kouchkovsky, MD
Assistant Clinical Professor
University of California, San Francisco