Hyperpolarized Pyruvate Injection in Subjects With Prostate Cancer

NCT01229618 | Completed Phase 1 DMC

• 1 other identifier: 085517
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Current imaging options do not assess prostate cancer well. This study will combine two magnetic resonance imaging modalities, MRI and MRSI, in order to determine the utility to physicians and patients with prostate cancer in making treatment decisions and seeing how well various types of treatment work. Hyperpolarized pyruvate (13C) is an investigational product that may enhance the imaging capability of MRI and MRSI. Hyperpolarized pyruvate will be injected into the body to determine how it is metabolized and how it's metabolism can be assessed using MR imaging. The purpose of this study is to determine the safety and metabolism of hyperpolarized pyruvate in humans, and how this can be used to increase the effectiveness of MR imaging with regards to patient care.

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability.

  Assessment of the occurrence of clinically significant changes in safety variables from baseline. Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Monitoring will occur to evaluate for dose-limiting toxicity. Dose-Limiting Toxicity (DLT) is defined as any toxicity greater than or equal to grade 2, 3 or 4, attributable to the imaging agent and occurring within 7 days after administration. The maximum tolerated dose will be the dose level at which \<33% DLT occurs.

  7 days

Secondary Outcomes (2)

• to determine the time course and imaging window that provides the best signal-to-noise ratio (SNR) of the presence of hyperpolarized pyruvate (13C).

• To determine the kinetics and prostate metabolism of hyperpolarized pyruvate (13C)

Study Arms (3)

1

EXPERIMENTAL

0.14 ml/kg bw - hyperpolarized pyruvate

Drug: Hyperpolarized Pyruvate (13C) injection

2

EXPERIMENTAL

0.28 ml/kg bw - hyperpolarized pyruvate

Drug: Hyperpolarized Pyruvate (13C) injection

3

EXPERIMENTAL

0.43 ml/kg bw - hyperpolarized pyruvate

Drug: Hyperpolarized Pyruvate (13C) injection

Interventions

Hyperpolarized Pyruvate (13C) injection DRUG

single hyperpolarized pyruvate IV (intravenous) injection followed by MR imaging scans (MRI and MRSI)

Also known as: [1-13C]pyruvic acid, AH111710

1; 2; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has biopsy-proven prostate cancer and is either undergoing active surveillance ("watchful waiting") or pre primary local treatment for prostate cancer (i.e., prior to either radiation therapy or radical prostatectomy).
• The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
• The subject has concordant MRI/1H MRSI findings from a prior MR staging exam performed within 8 weeks of the 13C MRSI exam performed in this study with IMP, or is willing to undergo MRI/1H MRSI in connection with the study exam.
• Negative test for hepatitis B and hepatitis C.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Laboratory criteria for protocol entry:
• Absolute neutrophil count (ANC) \>/= 1500 cells/microLiters
• Hemoglobin \>/= 9.0 gm/dL
• Platelets \>/= 100,000 cells/microLiters
• Estimated creatinine clearance \>/= 60 mL/min (by the Cockcroft Gault equation)
• Bilirubin within normal range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within normal range
• Willing to use contraception during and for 1 month after completion of the study.

You may not qualify if:

• Current or prior androgen deprivation therapy; previous use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least 1 month prior to study entry.
• Poorly controlled hypertension, with blood pressure at study entry \>150/90.
• Contraindication for or inability to tolerate MRI examination.
• Prostate biopsy within 12 weeks prior to study entry.
• BMI of less than 18.5 or greater than 32. At the 0.43 ml/kg dose, subject body weight should be less than or equal to 100 kg owing to limitations in the amount of IMP available.
• Congestive heart failure or New York Heart Association (NYHA) status \>2.
• A past or present medical history of clinically significant electrocardiogram (EKG) abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) less than 1 year ago with ensuing unstable EKG.
• Ongoing acute or chronic pulmonary bronchospastic disease, including a history of chronic obstructive pulmonary disease or asthma, with an exacerbation within the past year.

Sponsors & Collaborators

• University of California, San Francisco: lead
• GE Healthcare: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (5)

• Albers MJ, Bok R, Chen AP, Cunningham CH, Zierhut ML, Zhang VY, Kohler SJ, Tropp J, Hurd RE, Yen YF, Nelson SJ, Vigneron DB, Kurhanewicz J. Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Cancer Res. 2008 Oct 15;68(20):8607-15. doi: 10.1158/0008-5472.CAN-08-0749.

  PMID: 18922937 BACKGROUND

• Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K. Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10158-63. doi: 10.1073/pnas.1733835100. Epub 2003 Aug 20.

  PMID: 12930897 BACKGROUND

• Hricak H, Choyke PL, Eberhardt SC, Leibel SA, Scardino PT. Imaging prostate cancer: a multidisciplinary perspective. Radiology. 2007 Apr;243(1):28-53. doi: 10.1148/radiol.2431030580.

  PMID: 17392247 BACKGROUND

• Swanson MG, Zektzer AS, Tabatabai ZL, Simko J, Jarso S, Keshari KR, Schmitt L, Carroll PR, Shinohara K, Vigneron DB, Kurhanewicz J. Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy. Magn Reson Med. 2006 Jun;55(6):1257-64. doi: 10.1002/mrm.20909.

  PMID: 16685733 BACKGROUND

• Tessem MB, Swanson MG, Keshari KR, Albers MJ, Joun D, Tabatabai ZL, Simko JP, Shinohara K, Nelson SJ, Vigneron DB, Gribbestad IS, Kurhanewicz J. Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues. Magn Reson Med. 2008 Sep;60(3):510-6. doi: 10.1002/mrm.21694.

  PMID: 18727052 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Injections

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Charles Ryan, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Medicine and Urology

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 28, 2010
• Study Start: October 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: August 1, 2013
• Last Updated: October 5, 2015

Record last verified: 2014-08

Locations

US (1)