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Hyperpolarized Pyruvate (13C) MR Imaging in Monitoring Patients With Prostate Cancer on Active Surveillance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03933670
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : April 30, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
Information provided by (Responsible Party):
Rahul Aggarwal, University of California, San Francisco

Brief Summary:
This phase II trial studies the side how well hyperpolarized carbon C 13 pyruvate (HP C-13 pyruvate) magnetic resonance imaging (MRI) works in monitoring patients with prostate cancer on active surveillance who have not received treatment. Diagnostic procedures, such as MRI, may help visualize HP C-13 pyruvate uptake and breakdown in tumor cells.

Condition or disease Intervention/treatment Phase
Prostate Adenocarcinoma Drug: Hyperpolarized Carbon C 13 Pyruvate Procedure: Magnetic Resonance Spectroscopic Imaging Procedure: MRI Ultrasound Fusion Guided Biopsy Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral conversion of HP 13C pyruvate to lactate (kPL) and HP 13C pyruvate to glutamate (kPG) in regions of tumor versus (vs.) adjacent benign tissue as assessed by multi-parametric MRI (mpMRI) imaging characteristics. (Part 1) II. Determine the association between intra-tumoral kPL and kPG with Gleason grade determined during magnetic resonance (MR)/ultrasound (US)-guided fusion prostate biopsies obtained within 6 months following baseline HP C-13 pyruvate MR exam. (Part 2)

SECONDARY OBJECTIVES:

I. Evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies.

II. Determine the association between peak intra-tumoral kPL observed on baseline imaging with serum prostate specific antigen (PSA).

III. 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.

IV. Describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP C-13 MR exam.

V. Further characterize the safety profile of HP C-13 pyruvate injections.

EXPLORATORY OBJECTIVES:

I. Correlate peak intra-tumoral kPL with results of gene expression profiling using DECIPHER assay.

II. Correlate peak intra-tumoral kPL and kPG with DECIPHER GRID tumor ribonucleic acid (RNA) expression of relevant components of the glycolytic pathway including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), aconitate hydratase (aconitase), myelocytomatosis oncogene (MYC), monocarboxylate transporter 4 (MCT4) (lactate transporter).

III. For patients who undergo optional follow-up HP C-13 pyruvate/MRI 6-15 months following baseline scan, determine the mean percent change from baseline in intra-tumoral kPL and kPG and whether the change from baseline is associated change in clinical risk assessment as determined by University of California, San Francisco (UCSF)-Cancer of the Prostate Risk Assessment (CAPRA) risk score.

OUTLINE:

Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than one minute, then undergo magnetic resonance spectroscopic imaging (MRSI) after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.

After completion of study, patients will be followed up periodically.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Phase 2 Study of Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) in Patients With Prostate Cancer on Active Surveillance
Actual Study Start Date : July 18, 2018
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Diagnostic (HP C-13 MRI)
Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute, then undergo MRSI after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.
Drug: Hyperpolarized Carbon C 13 Pyruvate
Given IV
Other Names:
  • Hyperpolarized 13C-Pyruvate
  • Hyperpolarized Pyruvate (13C)

Procedure: Magnetic Resonance Spectroscopic Imaging
Undergo MRSI
Other Names:
  • Hydrogen-1 (1H)- Nuclear Magnetic Resonance Spectroscopic Imaging
  • 1H-nuclear magnetic resonance spectroscopic imaging
  • Magnetic Resonance Spectroscopy
  • MRS
  • MRS Imaging
  • MRSI
  • Proton Magnetic Resonance Spectroscopic Imaging

Procedure: MRI Ultrasound Fusion Guided Biopsy
Undergo MR/US fusion-guided prostate biopsy
Other Names:
  • Fusion Biopsy
  • Fusion Guided Biopsy
  • Fusion-Guided Biopsy
  • MR Fusion Biopsy
  • MRI-Ultrasound Fusion Biopsy
  • MRI/Ultrasound Fusion Biopsy
  • MRI/US Biopsy




Primary Outcome Measures :
  1. Signal-to-noise ratio (SNR) of hyperpolarized lactate [ Time Frame: At Baseline ]
    Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics.

  2. Intra-tumoral C-pyruvate to lactate (kPL) [ Time Frame: At Baseline ]
    Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics

  3. Intra-tumoral C-pyruvate to glutamate (kPG) [ Time Frame: At Baseline ]
    Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics

  4. Association between intra-tumoral C-pyruvate to lactate (kPL) with Gleason grade [ Time Frame: Within 12 weeks following baseline HP C-13 pyruvate MR exam ]
    kPL will be compared with the pathologic Gleason grade determined using tissue from an MR/US-guided fusion prostate biopsy. Measured kPL will be compared by pathologic Gleason grade using an ANOVA model. If there is an overall difference, the Newman-Keuls post hoc test will be used to determine which tissue pairs differ.

  5. Association between intra-tumoral C-pyruvate to glutamate (kPG) with Gleason grade [ Time Frame: Within 12 weeks following baseline HP C-13 pyruvate MR exam ]
    kPG will be compared with the pathologic Gleason grade determined using tissue from an MR/US-guided fusion prostate biopsy. Measured kPG will be compared by pathologic Gleason grade using an ANOVA model. If there is an overall difference, the Newman-Keuls post hoc test will be used to determine which tissue pairs differ.


Secondary Outcome Measures :
  1. Intra-patient variability in kPL [ Time Frame: Up to 15 months ]
    Intra-patient variability in the kPL will be summarized by the intraclass correlation and presented with a 90% confidence interval.

  2. Intra-patient variability in kPG [ Time Frame: Up to 15 months ]
    Intra-patient variability in the kPG will be summarized by the intraclass correlation and presented with a 90% confidence interval.

  3. Contrast between kPL and kPG in regions of tumor [ Time Frame: Up to 15 months ]
    The kPL and kPG will be contrasted in regions of tumor. Determined with prostate imaging reporting and data system (PI-RADS) version 2 classification score (1 through 5)

  4. Comparison of kPL and kPG with apparent diffusion coefficient in region of tumor [ Time Frame: Up to 15 months ]
    The kPL and kPG will be compared with apparent diffusion coefficient in region of tumor. Determined by comparison to peak intra-tumoral apparent diffusion coefficient (ADC) value

  5. Incidence of adverse events graded [ Time Frame: Up to 15 months ]
    According to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  6. Association between peak intra-tumoral kPL observed on baseline imaging with serum PSA [ Time Frame: At Baseline ]
    Determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. The study cohort will be dichotomized by mean intra-tumoral kPL above and below the median and the mean serum PSA will be compared between the two dichotomized subgroups using Mann-Whitney test.

  7. Describe frequency of up-grading of tumor [ Time Frame: Within 12 weeks following baseline HP C-13 pyruvate MR exam ]
    Describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP C-13 MR exam



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has biopsy-proven adenocarcinoma of the prostate with low to intermediate risk disease by UCSF-CAPRA scoring at study entry
  • For Part 1: Patient planning to enroll or currently on active surveillance; For Part 2: Currently enrolled on active surveillance with planned fusion biopsy within 12 weeks following completion of baseline HP C-13 pyruvate/mpMRI on study
  • The subject 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
  • Absolute neutrophil count (ANC) >= 1000 cells/microliter (uL)
  • Hemoglobin >= 9.0 gm/deciliter (dL)
  • Platelets >= 75,000 cells/uL
  • Estimated creatinine clearance* >= 50 milliliter (mL)/min

    • by the Cockcroft Gault equation
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or if =< 4 gm/dL and direct bilirubin is within normal limit (WNL)
  • Aspartate aminotransferase (AST) =< 1.5 x ULN
  • Alanine aminotransferase (ALT) =< 1.5 x ULN

Exclusion Criteria:

  • Patients without evidence of any prostate cancer on most recent prostate biopsy performed prior to study entry
  • Current or prior androgen deprivation therapy including luteinizing hormone-releasing hormone (LHRH) analogue or oral anti-androgen therapy. Previous use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least 28 days prior to baseline C-13 HP pyruvate MRI
  • Prior radiation treatment of the prostate
  • 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 mmg 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03933670


Contacts
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Contact: Christopher Sotto (415) 353-9452 Christopher.Sotto@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Rahul R. Aggarwal, MD    877-827-3222    cancertrials@ucsf.edu   
Principal Investigator: Rahul R. Aggarwal, MD         
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
Investigators
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Principal Investigator: Rahul R Aggarwal, MD University of California, San Francisco
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Responsible Party: Rahul Aggarwal, Associate Clinical Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03933670    
Other Study ID Numbers: 175516
NCI-2018-02195 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA082103 ( U.S. NIH Grant/Contract )
R01CA211150 ( U.S. NIH Grant/Contract )
R01EB017449 ( U.S. NIH Grant/Contract )
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: April 30, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Adenocarcinoma
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type