Prostate CancerPhase 1/2NCT02913131
Hyperpolarized C-13 Pyruvate as a Biomarker in Patients With Advanced Solid Tumor Malignancies
A Phase 1/2 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 single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate as a Biomarker of PI3K/mTOR pathway inhibition in patients with advanced solid tumor malignancies. 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
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2016to 5 Apr 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Presence of at least one target liver or other intra-abdominal lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging: Target lesion must measure >=1.0 cm in long axis diameter on CT or MRI
- 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 creatinine < 1.5 x ULN or estimated creatinine clearance >=500 mL/min (by the Cockcroft Gault equation) and total bilirubin <3x upper limit of normal (ULN).
- Part B only:
- No prior local therapy to target lesion.
Show all 11Show fewer
- If patient agrees to optional biopsy:
- Presence of at least one target lesion amenable to percutaneous tumor biopsy in the judgment of Interventional Radiology
- No history of bleeding diathesis.
- Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy.
- Planned treatment with agent targeting PI3K/mTOR pathway (either standard of care or investigational agent)
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 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, 94143
About this study
Official title: Hyperpolarized C-13 Pyruvate as a Biomarker of PI3K/mTOR Pathway Inhibition in Patients With Advanced Solid Tumor Malignancies
This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate as a Biomarker of PI3K/mTOR pathway inhibition in patients with advanced solid tumor malignancies. The current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of PI3K/mTOR pathway inhibitors (e.g. CUDC-907, BYL719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the PI3K/mTOR signaling pathway (eg. everolimus).
Read the detailed description
This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate/metabolic magnetic resonance (MR) imaging. The current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of PI3K/mTOR pathway inhibitors (e.g. CUDC-907, BYL719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the PI3K/mTOR signaling pathway (eg. everolimus).
In Part A (run-in feasibility phase), patients will undergo imaging at a single time point, without paired tumor biopsy. There will be no follow up imaging or requirement for treatment with PI3K/mTOR pathway inhibitor. Iterative adjustment of radiofrequency coil geometry and imaging sequences will be undertaken to optimize intra-tumoral hyperpolarized pyruvate/lactate signal-to-noise ratio.
In Part B, patients will undergo paired baseline hyperpolarized C-13 pyruvate imaging + tumor biopsy,then initiate treatment with agent inhibiting the PI3K/mTOR pathway. After 21 days (+/- 14 days), patients will undergo repeat hyperpolarized C-13 pyruvate MR imaging + tumor biopsy. Patients will subsequently be treated with PI3K/mTOR pathway inhibitor until disease progression, unacceptable toxicity, or patient/physician decision to discontinue therapy.
- 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
Pyruvate injection followed by an MRI scan.
MRIDevice
MRI scan following the pyruvate (13c) injection
| Study group | Role | What they receive |
|---|---|---|
| Part A: Feasibility Run-In | Experimental | Patients with advanced solid tumor malignancies with at least one liver metastasis will be enrolled with iterative adjustment of coil design to optimize imaging parameters including spatial resolution and signal-to-noise ratio (SNR) of hyperpolarized pyruvate / lactate within the target metastatic lesion(s). Receives: Drug: Pyruvate (13C); Device: MRI |
| Part B: Biomarker Cohort | Experimental | Patients with advanced solid tumor malignancies and the presence of at least one liver metastasis amenable to hyperpolarized C-13 pyruvate metabolic MR imaging who are planning on being treated with agent targeting PI3K/mTOR pathway will be enrolled. Receives: Drug: Pyruvate (13C); Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Signal-to-noise Ratio (Part A)
The Signal-to-noise ratio with respect to intra-tumoral hyperpolarized (HP) C-13 Lactate/Pyruvate (lac/pyr) ratio detected within target liver or other intra-abdominal metastasis in patients with advanced solid tumor malignancies enrolled in the feasibility cohort will be determined
Measured: 1 day
Mean Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio (Part B)
Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio after initiation of treatment with PI3K/mTOR pathway inhibitor for participants enrolled in the biomarker cohort, along with 95% confidence interval.
Measured: Up to 24 months
Secondary outcomes (3)
Number of Participants With Reported Treatment-related Adverse Events
Number of participants with documented treatment-related adverse events will be reported for all patients having received a single dose of HP C-13 pyruvate. The study will use the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 for reporting of adverse events that occur within 3 days of each imaging procedure over the course of the study and any biopsy-related adverse events.
Measured: Up to 24 months
Association Between Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio on Metabolic MR Imaging With Clinical Benefit Rate (Part B)
For the purposes of analyzing the association between percent change from baseline in intra-tumoral peak lactate/pyruvate ratio on HP MRI with subsequent clinical outcomes, the cohort will be dichotomized by the median percent change. The objective response rate by RECIST 1.1 criteria and clinical benefit rate (response or stable disease for > 24 weeks) will be compared between dichotomized groups using the chi-squared test.
Measured: Up to 24 months
Association Between Percent Change From Baseline in Peak Intra-humoral HP Lactate/Pyruvate Ratio on Metabolic MR Imaging With Progression-free Survival (Part B)
The cohort will be dichotomized by the median percent change. The log-rank test statistic will then be used to test the association of estimates of the hazard functions of the two groups at each observed event time by computing the observed and expected number of events in one of the groups at each observed event time and then adding these to obtain an overall summary across all-time points where there is an event.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study start20 Oct 2016
- Primary completion5 Apr 2021
- Study completion5 Apr 2021
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rahul Aggarwal
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), 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
- NCT02913131
- Sponsor's protocol ID
- 159517
- Other IDs
- R01CA183071, NCI-2017-02190
- Status last verified
- Mar 2022
- First submitted
- 20 Sep 2016
- Last updated
- 22 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- 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 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperpolarized C-13 Pyruvate as a Biomarker of PI3K/mTOR Pathway Inhibition in Patients With Advanced Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT02913131
- Acronym / sponsor ID
- 159517
- Conditions
- Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Rahul AggarwalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 20 Oct 2016 (actual)
- Primary completion
- 5 Apr 2021 (actual)
- Study completion
- 5 Apr 2021 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Posted 22 Apr 2022
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 single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate as a Biomarker of PI3K/mTOR pathway inhibition in patients with advanced solid tumor malignancies. The current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of PI3K/mTOR pathway inhibitors (e.g. CUDC-907, BYL719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the PI3K/mTOR signaling pathway (eg. everolimus).
Detailed description
This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate/metabolic magnetic resonance (MR) imaging. The current protocol will serve as a companion imaging biomarker study paired with therapeutic trials of PI3K/mTOR pathway inhibitors (e.g. CUDC-907, BYL719), as well as a stand-alone protocol for patients treated with standard-of-care therapies inhibiting the PI3K/mTOR signaling pathway (eg. everolimus).
In Part A (run-in feasibility phase), patients will undergo imaging at a single time point, without paired tumor biopsy. There will be no follow up imaging or requirement for treatment with PI3K/mTOR pathway inhibitor. Iterative adjustment of radiofrequency coil geometry and imaging sequences will be undertaken to optimize intra-tumoral hyperpolarized pyruvate/lactate signal-to-noise ratio.
In Part B, patients will undergo paired baseline hyperpolarized C-13 pyruvate imaging + tumor biopsy,then initiate treatment with agent inhibiting the PI3K/mTOR pathway. After 21 days (+/- 14 days), patients will undergo repeat hyperpolarized C-13 pyruvate MR imaging + tumor biopsy. Patients will subsequently be treated with PI3K/mTOR pathway inhibitor until disease progression, unacceptable toxicity, or patient/physician decision to discontinue therapy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: Feasibility Run-In | Experimental | Drug: Pyruvate (13C), Device: MRIPatients with advanced solid tumor malignancies with at least one liver metastasis will be enrolled with iterative adjustment of coil design to optimize imaging parameters including spatial resolution and signal-to-noise ratio (SNR) of hyperpolarized pyruvate / lactate within the target metastatic lesion(s). |
| Part B: Biomarker Cohort | Experimental | Drug: Pyruvate (13C), Device: MRIPatients with advanced solid tumor malignancies and the presence of at least one liver metastasis amenable to hyperpolarized C-13 pyruvate metabolic MR imaging who are planning on being treated with agent targeting PI3K/mTOR pathway will be enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Presence of at least one target liver or other intra-abdominal lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging: Target lesion must measure >=1.0 cm in long axis diameter on CT or MRI
- 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 creatinine < 1.5 x ULN or estimated creatinine clearance >=500 mL/min (by the Cockcroft Gault equation) and total bilirubin <3x upper limit of normal (ULN).
- No prior local therapy to target lesion.
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 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)Pyruvate injection followed by an MRI scan. | Drug | Part A: Feasibility Run-In, Part B: Biomarker Cohort |
| MRIMRI scan following the pyruvate (13c) injection | Device | Part A: Feasibility Run-In, Part B: Biomarker Cohort |
Primary outcome
Signal-to-noise Ratio (Part A)
Time frame: 1 day
The Signal-to-noise ratio with respect to intra-tumoral hyperpolarized (HP) C-13 Lactate/Pyruvate (lac/pyr) ratio detected within target liver or other intra-abdominal metastasis in patients with advanced solid tumor malignancies enrolled in the feasibility cohort will be determined
Mean Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio (Part B)
Time frame: Up to 24 months
Descriptive statistics will be used to characterize the mean change from baseline in intra-tumoral HP pyruvate/lactate ratio after initiation of treatment with PI3K/mTOR pathway inhibitor for participants enrolled in the biomarker cohort, along with 95% confidence interval.
3 secondary outcomes
Number of Participants With Reported Treatment-related Adverse Events
Time frame: Up to 24 months
Association Between Percent Change From Baseline in Peak Intra-tumoral Hyperpolarized Lactate/Pyruvate Ratio on Metabolic MR Imaging With Clinical Benefit Rate (Part B)
Time frame: Up to 24 months
Association Between Percent Change From Baseline in Peak Intra-humoral HP Lactate/Pyruvate Ratio on Metabolic MR Imaging With Progression-free Survival (Part B)
Time frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 1/2 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 11 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 22 Apr 2022. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Signal-to-noise Ratio (Part A) (time frame: 1 day). The study lists 2 primary outcomes in all. 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 22 Apr 2022.