Prostate CancerPhase 1NCT01229618
Hyperpolarized Pyruvate Injection in Subjects With Prostate Cancer
A Phase 1 study testing Hyperpolarized Pyruvate (13C) injection in people with Prostate Cancer, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Hyperpolarized Pyruvate (13C) injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Aug 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- The subject has received, or is scheduled to receive, another IMP from 1 month before to 1 month after inclusion in this study.
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase 1 Ascending-dose Study to Assess the Safety and Tolerability and Imaging Potential of Hyperpolarized Pyruvate (13C) Injection in Subjects With Prostate Cancer
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.
Read the detailed description
This is a phase 1 clinical study of an investigational medicinal product (IMP), hyperpolarized Pyruvate (13C) Injection. The study includes the acquisition of magnetic resonance (MR) data and will be performed in men with prostate cancer and intact prostates.
A standard dose-escalation design will be used; initially, 6 subjects will receive IMP at each dose level. As data on both the dynamics of arrival of the IMP and potential imaging efficacy are needed at each dose level, requiring the use of separate MR acquisition sequences, a modified 3+3 design will be applied in each dose cohort. The first 3 subjects will undergo dynamic 13C imaging to define the kinetics of delivery and metabolism of IMP, and the second 3 subjects will undergo 13C MR spectroscopic imaging (MRSI) to obtain 3-dimensional (3-D) spatial information about metabolism of IMP in regions of the prostate with and without cancer involvement.
After the apparent maximum tolerated dose (MTD) has been established, there will be an expansion of the 3-D imaging cohort to 6 subjects (9 subjects in total at this dose level) to obtain additional information regarding safety at the MTD. If >2 subjects from this cohort of 9 subjects experience a dose-limiting toxicity (DLT), the next lower dose will be defined as the MTD. At the dose level with the highest contrast to noise ratio (dose level less than or equal to the MTD) there will be an expansion of the imaging cohort to include another 15 subjects for a total of 18 subjects who undergo 13C 3-D scanning at this dose, to obtain exploratory information concerning the time course and SNR (signal to noise ratio) of the presence of hyperpolarized [1 13C] pyruvate and its metabolites in regions of cancer and benign prostate tissues. The information provided by these data will be used to develop the MR imaging protocol for future clinical trials that will seek to address the sensitivity and specificity of the technology.
- Conditions
- Prostate Cancer
- Being tested
- Hyperpolarized Pyruvate (13C) injection
- Keywords
- Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperpolarized Pyruvate (13C) injectionDrug
Also called [1-13C]pyruvic acid, AH111710
single hyperpolarized pyruvate IV (intravenous) injection followed by MR imaging scans (MRI and MRSI)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 0.14 ml/kg bw - hyperpolarized pyruvate Receives: Drug: Hyperpolarized Pyruvate (13C) injection |
| 2 | Experimental | 0.28 ml/kg bw - hyperpolarized pyruvate Receives: Drug: Hyperpolarized Pyruvate (13C) injection |
| 3 | Experimental | 0.43 ml/kg bw - hyperpolarized pyruvate Receives: Drug: Hyperpolarized Pyruvate (13C) injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
The optimum 13C imaging window for maximizing lactate SNR will be determined as the period of time after injection in which hyperpolarized lactate reaches a maximal plateau in the prostate. This plateau results from opposing processes of lactate production from pyruvate and T1 decay (for pre-clinical studies this plateau occurred approximately between 35 and 55 seconds).
To determine the kinetics and prostate metabolism of hyperpolarized pyruvate (13C)
For the subjects receiving 3-D 13C spectroscopic imaging (the second 3 subjects per dose cohort as well as the expansion cohorts), a fast 13C MRSI sequence will be used to acquire data from the prostate at a time defined by the kinetic studies (approximately 40 seconds after intravenous administration of hyperpolarized pyruvate).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionNov 2011
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- GE Healthcare
- Responsible party
- Principal investigator, Charles Ryan, University of California, San Francisco
- Investigators
- Charles Ryan, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01229618
- Sponsor's protocol ID
- 085517
- Status last verified
- Aug 2014
- First submitted
- 13 Oct 2010
- Last updated
- 5 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18922937Ardenkjaer-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.
PubMed 12930897Hricak 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.
PubMed 17392247Swanson 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.
PubMed 16685733Tessem 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.
PubMed 18727052
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Ascending-dose Study to Assess the Safety and Tolerability and Imaging Potential of Hyperpolarized Pyruvate (13C) Injection in Subjects With Prostate Cancer
- ClinicalTrials.gov ID
- NCT01229618
- Acronym / sponsor ID
- 085517
- Conditions
- Prostate Cancer
- Keywords
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- GE Healthcare
- Study start
- Oct 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 28 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase 1 clinical study of an investigational medicinal product (IMP), hyperpolarized Pyruvate (13C) Injection. The study includes the acquisition of magnetic resonance (MR) data and will be performed in men with prostate cancer and intact prostates.
A standard dose-escalation design will be used; initially, 6 subjects will receive IMP at each dose level. As data on both the dynamics of arrival of the IMP and potential imaging efficacy are needed at each dose level, requiring the use of separate MR acquisition sequences, a modified 3+3 design will be applied in each dose cohort. The first 3 subjects will undergo dynamic 13C imaging to define the kinetics of delivery and metabolism of IMP, and the second 3 subjects will undergo 13C MR spectroscopic imaging (MRSI) to obtain 3-dimensional (3-D) spatial information about metabolism of IMP in regions of the prostate with and without cancer involvement.
After the apparent maximum tolerated dose (MTD) has been established, there will be an expansion of the 3-D imaging cohort to 6 subjects (9 subjects in total at this dose level) to obtain additional information regarding safety at the MTD. If >2 subjects from this cohort of 9 subjects experience a dose-limiting toxicity (DLT), the next lower dose will be defined as the MTD. At the dose level with the highest contrast to noise ratio (dose level less than or equal to the MTD) there will be an expansion of the imaging cohort to include another 15 subjects for a total of 18 subjects who undergo 13C 3-D scanning at this dose, to obtain exploratory information concerning the time course and SNR (signal to noise ratio) of the presence of hyperpolarized [1 13C] pyruvate and its metabolites in regions of cancer and benign prostate tissues. The information provided by these data will be used to develop the MR imaging protocol for future clinical trials that will seek to address the sensitivity and specificity of the technology.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Hyperpolarized Pyruvate (13C) injection0.14 ml/kg bw - hyperpolarized pyruvate |
| 2 | Experimental | Drug: Hyperpolarized Pyruvate (13C) injection0.28 ml/kg bw - hyperpolarized pyruvate |
| 3 | Experimental | Drug: Hyperpolarized Pyruvate (13C) injection0.43 ml/kg bw - hyperpolarized pyruvate |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (9 listed)
- The subject has received, or is scheduled to receive, another IMP from 1 month before to 1 month after inclusion in this study.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperpolarized Pyruvate (13C) injectionAlso: [1-13C]pyruvic acid, AH111710single hyperpolarized pyruvate IV (intravenous) injection followed by MR imaging scans (MRI and MRSI) | Drug | 1, 2, 3 |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
Time frame: 7 days
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.
2 secondary outcomes
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2015.
- Background: PubMed 18922937Albers 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.
- Background: PubMed 12930897Ardenkjaer-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.
- Background: PubMed 17392247Hricak 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.
- Background: PubMed 16685733Swanson 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.
- Background: PubMed 18727052Tessem 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Ryan, M.D. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hyperpolarized Pyruvate (13C) injection in people with Prostate Cancer, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability. (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01229618, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2015.