Pilot Study of (MR) Imaging With Pyruvate (13C) to Detect High Grade Prostate Cancer

Официальное название

A Pilot Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) to Detect High Grade Localized Prostate Cancer

Обзор

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

Подробное описание

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.

II. To determine the optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr), lac/pyr area under the curve (AUC), 13C pyruvate to lactate (kPL) rate, urea AUC, and urea transfer constant (ktrans) on magnetic resonance imaging (MRI) that accurately detects primary Gleason 4 component cancer (Cohort A).

III. To determine the optimal cut-off value of peak lac/pyr, lac/pyr AUC, kPL Urea AUC, Urea ktrans and kPL-urea product (kUP) on MRI that accurately detects in-field clinically significant (ie. Gleason score \>3+3) recurrent/residual prostate cancer (Cohort B only).

IV. To determine the reproducibility of peak lac/pyr, lac/pyr AUC and kPL, urea AUC and urea transfer constant (ktrans) with same-day repeated dose studies. with same-day repeated dose studies.

V. To compare peak lac/pyr, lac/pyr AUC and kPL, urea AUC, urea transfer constant (ktrans) on MRI with Prostate Imaging-Reporting and Data System (PI-RADS) assessment of multiparametric MRI in predicting regions of cancer versus benign tissue.

EXPLORATORY OBJECTIVES:

I. To correlate histologic markers, including lactate dehydrogenase A (LDHA) expression and activity level, along with Ki-67, MYC, and MCT 1 and 4 expression, with peak intra-tumoral lac/pyr ratio, lactate AUC, and kPL detected using anatomically aligned magnetic resonance (MR) cross-sectional images of the prostate gland.

II. To test for an association between mean intra-tumoral lac/pyr signal and lactate AUC, kPL, urea AUC, and urea transfer constant (ktrans) with adverse clinical and pathologic characteristics including extracapsular extension, positive nodal involvement, and failure to achieve undetectable prostate specific antigen (PSA) nadir following prostatectomy.

OUTLINE:

Participants receive either hyperpolarized carbon pyruvate (13C) or co-polarized 13C pyruvate and 13C, 15N2urea intravenously (IV) and undergo MRSI within 12 weeks of undergoing non-investigational radical prostatectomy (cohort A) or non-investigational systematic and MR-targeted biopsies (cohort B). Participants may receive optional second hyperpolarized 13C injection and dynamic 13C MRI scan performed within 15 to 60 minutes following completion of first scan.

After completion of study, participants are followed up at 24 hours.

Вмешательства

• Препарат Hyperpolarized 13C-Pyruvate
  Given IV
• Препарат Hyperpolarized 13C,15N2-urea
  Given IV
• Процедура Magnetic Resonance Spectroscopic Imaging
  Undergo MRSI

Первичные конечные точки

• Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio by pathological grade (Cohort A) [Срок оценки: Baseline, 1 day]
• Mean peak intra-tumoral lactate/pyruvate (lac/pyr) ratio (Cohort B) [Срок оценки: Baseline, 1 day]
• Mean lactate area under curve (AUC) by pathological grade (Cohort A) [Срок оценки: Baseline, 1 day]
• Mean lactate area under curve (AUC) (Cohort B) [Срок оценки: Baseline, 1 day]
• Mean peak conversion of HP 13C pyruvate to lactate (kPL) by pathological grade (Cohort A) [Срок оценки: Baseline, 1 day]
• Mean peak conversion of HP 13C pyruvate to lactate (kPL) (Cohort B) [Срок оценки: Baseline, 1 day]
• Mean Urea AUC by pathological grade (Cohort A) [Срок оценки: Baseline, 1 day]
• Mean Urea AUC (Cohort B) [Срок оценки: Baseline, 1 day]
• Mean urea transfer constant (Ktrans) by pathological grade (Cohort A) [Срок оценки: Baseline, 1 day]
• Mean urea transfer constant (Ktrans) (Cohort B) [Срок оценки: Baseline, 1 day]

Вторичные конечные точки (12)

• Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort A) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of peak lactate to pyruvate ratio (lac/pyr) (Cohort B) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort A) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of lac/pyr area under the curve (AUC) (Cohort B) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort A) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of 13C pyruvate to lactate (kPL) rate (Cohort B) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of urea AUC (Cohort A) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of urea AUC (Cohort B) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of urea transfer constant (ktrans) (Cohort A) [Срок оценки: Baseline, 1 day]
• Optimal cut-off value of urea transfer constant (ktrans) (Cohort B) [Срок оценки: Baseline, 1 day]
• Proportion of participants with Treatment-Related Adverse Events [Срок оценки: Baseline, 1 day]
• Compare lactate/pyruvate area under curve (AUC) with Prostate Imaging Reporting and Data System (PI-RADS) [Срок оценки: Baseline, 1 day]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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 >= 2.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 1 центр

• University of California, San Francisco — San Francisco

Идентификаторы

NCT: NCT02526368 · 15557 · R01CA211150 · U01EB026412 · R01EB017449 · R01CA214554 · R01CA238379 · R01CA300053 · NCI-2015-02008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗