Prostate CancerPhase 1MRNCT02911467
Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (HP) (13C) in Castration-Resistant Prostate Cancer
A Phase 1 study testing Pyruvate (13C) and MRI in people with Prostate Cancer, run by Rahul Aggarwal at 1 site in United States.
Trial summary
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging with Hyperpolarized Pyruvate (HP) (13C) as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Pyruvate (13C) and MRI
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2016to 20 Jul 2020
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy-proven prostate cancer.
- Progressive, castration-resistant disease according to PCWG2 criteria.
- Planned treatment with an androgen signaling inhibitor (e.g., abiraterone, enzalutamide, apalutamide (ARN-509)). Patients must not be receiving androgen signaling inhibitor at the time of the baseline MR scan. Combination treatment (e.g., androgen signaling inhibitor in conjunction with another systemic treatment) is allowed.
- Presence of at least one target lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:
- Soft tissue/visceral organ target lesions must measure at 1.5 cm in long axis diameter on CT or MRI.
- Target lesions in the bone must be visualized by CT or MRI (lesions present only on bone scan do not qualify).
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- For patients with target lesion in prostate/prostatic bed:
- No contra-indications to endorectal coil insertion (e.g., patients with a prior abdominoperineal resection of the rectum or latex allergy).
- No prior local treatment to the selected lesion. Patients who have received prior radiation or ablative therapy to the prostate will be required to have biopsy-proven evidence of disease recurrence following completion of local therapy.
- 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.
- Adequate organ function, including absolute neutrophil count (ANC) ≥ 1500 cells/µL, hemoglobin ≥ 9.0 gm/dL, platelets ≥ 75,000 cells/µL, creatinine < 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min (by the Cockcroft Gault equation), bilirubin <1.5x ULN (unless Gilbert's is suspected in which case total bilirubin < 3 x ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5x ULN.
- For patients undergoing optional tumor biopsy:
- No history of bleeding diathesis.
- Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy.
- For patients with partners of childbearing potential, willing to use adequate contraception for one month after undergoing HP pyruvate infusion.
- Patients must have prior bilateral orchiectomy or be on continuous luteinizing-hormone releasing hormone (LHRH) analogue therapy for the duration of study.
- Castrate level of serum testosterone (< 50 ng/dL) at study entry.
Who cannot join
- Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- Patients unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
- Poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg. The addition of anti-hypertensives to control blood pressure is allowed.
- Congestive heart failure or New York Heart Association (NYHA) status ≥ 2.
- A history of clinically significant EKG abnormalities, including QT prolongation (QTcF > 500 ms), 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.
- Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94158
About this study
Official title: Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) as a Predictive Biomarker of Response to Androgen Signaling Inhibitors in Castration-Resistant Prostate Cancer
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging with Hyperpolarized Pyruvate (HP) (13C) as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer.
Read the detailed description
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer. Patients with a target lesion that is amenable for metabolic MR imaging will be eligible for study participation. Patients will undergo baseline metabolic MR imaging with Hyperpolarized Pyruvate C-13 pyruvate followed by initiation of androgen signaling inhibition (either as standard of care or as part of clinical trial; including abiraterone and/or enzalutamide treatment). Patient will subsequently undergo repeat metabolic MR scan after 28 days (+/- 7 days) of therapy. For those without primarily refractory disease, a third metabolic MR scan will be completed at the time of radiographic disease progression by The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria. MR- or CT-guided tumor biopsies are optional at baseline and at the time of disease progression.
- Conditions
- Prostate Cancer
- Being tested
- Pyruvate (13C), MRI
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyruvate (13C)Drug
Also called Hyperpolarized Pyruvate (13C)
Pyruvate injection followed by an MRI scan.
MRIDevice
Also called Magnetic Resonance Imaging
MRI scan following the Pyruvate injection
| Study group | Role | What they receive |
|---|---|---|
| MR imaging with hyperpolarized 13C pyruvate of men with CRPC | Experimental | 75 men with castration-resistant prostate cancer (CRPC) will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at baseline and after 1 month of treatment with an androgen signaling inhibitor. Patients with CRPC that is not primarily refractory (defined as disease progression by PCWG2 criteria within 6 months of treatment initiation) to Androgen Signaling Inhibitors (ASI) treatment will undergo a third metabolic MR scan at the time of disease progression. Patients may undergo optional MR- or CT-guided tumor biopsies at baseline and at the time of disease progression. Receives: Drug: Pyruvate (13C); Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean difference in baseline intra-tumoral peak lac/pyr ratio on HP C-13 MRI in ASI-refractory versus ASI-responsive CRPC tumors
ASI-refractory disease is defined as progression by PCWG2 criteria within 6 months of treatment initiation. ASI-responsive disease includes all other tumors not meeting this criterion. A two sample t-test will be used to compare the mean intra-tumoral HP lac/pyr ratio between treatment-refractory versus treatment-responsive tumors. If a non-parametric distribution is observed, a Mann-Whitney test may also be used to compare the two groups.
Measured: Up to 6 months
Secondary outcomes (5)
Association between change from baseline in peak intra-tumoral HP lac/pyr ratio after 28 days of ASI treatment with subsequent clinical outcomes on ASI treatment
For the purposes of analyzing the association between early change in lac/pyr ratio on HP MRI with subsequent clinical outcomes, the cohort will be dichotomized according to whether follow up scan 4 weeks (28 days) after starting treatment demonstrates increase versus decrease in peak intratumoral lac/pyr ratio compared to baseline. The Prostate-specific antigen (PSA) response rate (PCWG2 criteria) will be compared between dichotomized groups using the chi-squared test. The log rank test will be used to compare the radiographic progression-free survival between the two groups
Measured: Up to 28 days
Mean percent change from baseline in peak intra-tumoral HP lac/pyr ratio on repeat metabolic MRI
The mean percent change from baseline in peak intra-tumoral HP lac/pyr ratio to repeat metabolic MRI obtained at the time of radiographic disease progression by PCWG2 criteria will be descriptively reported for the entire study cohort and for the subgroups of patients with treatment- refractory and treatment-responsive prostate cance
Measured: Up to 6 months
Baseline peak intra-tumoral HP lac/pyr ratio cut-point that most accurately predicts for response versus refractoriness to subsequent ASI treatment
Receiver-operating-curve will be applied to determine the optimal cut-point of peak intra-tumoral lac/pyr values on MRI that accurately distinguish treatment-refractory versus treatment responsive prostate cancer.
Measured: Baseline
Frequency of clinically significant changes in safety variables over time
Safety endpoints include monitoring for the occurrence of treatment-emergent AEs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology (Toxicity) Criteria for Adverse Events (CTCAE) version 4.0
Measured: Up to 6 months
Mean Intra-patient reproducibility of HP lac/pyr ratio
Intra-patient reproducibility of HP lac/pyr ratio for patients who undergo repeated dose imaging studies, as descriptively reported using summary statistics
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study start8 Nov 2016
- Primary completion20 Jul 2020
- Study completion20 Jul 2020
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rahul Aggarwal
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Rahul Aggarwal, University of California, San Francisco
- Investigators
- Rahul Aggarwal, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02911467
- Sponsor's protocol ID
- 15559
- Other IDs
- 5R01CA166655-04
- Acronym
- MR
- Status last verified
- Jul 2020
- First submitted
- 19 Sep 2016
- Last updated
- 24 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) as a Predictive Biomarker of Response to Androgen Signaling Inhibitors in Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02911467
- Acronym / sponsor ID
- MR / 15559
- Conditions
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Rahul AggarwalUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Nov 2016 (actual)
- Primary completion
- 20 Jul 2020 (actual)
- Study completion
- 20 Jul 2020 (actual)
- First posted
- 22 Sep 2016 (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.
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging with Hyperpolarized Pyruvate (HP) (13C) as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer.
Detailed description
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer. Patients with a target lesion that is amenable for metabolic MR imaging will be eligible for study participation. Patients will undergo baseline metabolic MR imaging with Hyperpolarized Pyruvate C-13 pyruvate followed by initiation of androgen signaling inhibition (either as standard of care or as part of clinical trial; including abiraterone and/or enzalutamide treatment). Patient will subsequently undergo repeat metabolic MR scan after 28 days (+/- 7 days) of therapy. For those without primarily refractory disease, a third metabolic MR scan will be completed at the time of radiographic disease progression by The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria. MR- or CT-guided tumor biopsies are optional at baseline and at the time of disease progression.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MR imaging with hyperpolarized 13C pyruvate of men with CRPC | Experimental | Drug: Pyruvate (13C), Device: MRI75 men with castration-resistant prostate cancer (CRPC) will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at baseline and after 1 month of treatment with an androgen signaling inhibitor. Patients with CRPC that is not primarily refractory (defined as disease progression by PCWG2 criteria within 6 months of treatment initiation) to Androgen Signaling Inhibitors (ASI) treatment will undergo a third metabolic MR scan at the time of disease progression. Patients may undergo optional MR- or CT-guided tumor biopsies at baseline and at the time of disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Biopsy-proven prostate cancer.
- Progressive, castration-resistant disease according to PCWG2 criteria.
- Planned treatment with an androgen signaling inhibitor (e.g., abiraterone, enzalutamide, apalutamide (ARN-509)). Patients must not be receiving androgen signaling inhibitor at the time of the baseline MR scan. Combination treatment (e.g., androgen signaling inhibitor in conjunction with another systemic treatment) is allowed.
- Presence of at least one target lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:
- The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
Key exclusion criteria (7 listed)
- Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- Patients unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
- Poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg. The addition of anti-hypertensives to control blood pressure is allowed.
- Congestive heart failure or New York Heart Association (NYHA) status ≥ 2.
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 |
|---|---|---|
| Pyruvate (13C)Also: Hyperpolarized Pyruvate (13C)Pyruvate injection followed by an MRI scan. | Drug | MR imaging with hyperpolarized 13C pyruvate of men with CRPC |
| MRIAlso: Magnetic Resonance ImagingMRI scan following the Pyruvate injection | Device | MR imaging with hyperpolarized 13C pyruvate of men with CRPC |
Primary outcome
Mean difference in baseline intra-tumoral peak lac/pyr ratio on HP C-13 MRI in ASI-refractory versus ASI-responsive CRPC tumors
Time frame: Up to 6 months
ASI-refractory disease is defined as progression by PCWG2 criteria within 6 months of treatment initiation. ASI-responsive disease includes all other tumors not meeting this criterion. A two sample t-test will be used to compare the mean intra-tumoral HP lac/pyr ratio between treatment-refractory versus treatment-responsive tumors. If a non-parametric distribution is observed, a Mann-Whitney test may also be used to compare the two groups.
5 secondary outcomes
Association between change from baseline in peak intra-tumoral HP lac/pyr ratio after 28 days of ASI treatment with subsequent clinical outcomes on ASI treatment
Time frame: Up to 28 days
Mean percent change from baseline in peak intra-tumoral HP lac/pyr ratio on repeat metabolic MRI
Time frame: Up to 6 months
Baseline peak intra-tumoral HP lac/pyr ratio cut-point that most accurately predicts for response versus refractoriness to subsequent ASI treatment
Time frame: Baseline
Frequency of clinically significant changes in safety variables over time
Time frame: Up to 6 months
Mean Intra-patient reproducibility of HP lac/pyr ratio
Time frame: Up to 6 months
Results and safety
The study was stopped early (reason given: Low Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Individual participant dataSharing planned: No
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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.
Rahul Aggarwal, MD 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 Pyruvate (13C) and MRI in people with Prostate Cancer, run by Rahul Aggarwal 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 18 inclusion and 7 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: stopped early, as of the sponsor's last update on 24 Jul 2020. 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 was stopped early (reason given: Low Accrual). Results are not available in the source record.
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?
Mean difference in baseline intra-tumoral peak lac/pyr ratio on HP C-13 MRI in ASI-refractory versus ASI-responsive CRPC tumors (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2020.