Hyperpolarized (HP) 13C Pyruvate Magnetic Resonance Imaging (MRI) as a Response Monitoring Tool in Patients With High-Risk Prostate Cancer Receiving Neoadjuvant Therapy
Summary
This study will evaluate the use of hyperpolarized 13C MRI (HP 13C MRI) and the HP-derived 13C pyruvate-to-lactate conversion rate constant (kPL) as an early response biomarker in men with treatment-naïve, high-risk, localized or locally advanced prostate cancer receiving neoadjuvant therapy.
Detailed description
PRIMARY OBJECTIVE: I. To investigate on-treatment changes in HP 13C MRI derived kPL as an early response biomarker in men with high-risk localized or locally advanced prostate cancer receiving neoadjuvant abiraterone/prednisone prior to radical prostatectomy (RP). SECONDARY OBJECTIVES: I. To evaluate the pathologic complete response/minimal residual disease rate at the time of radical prostatectomy following 12 weeks of neoadjuvant abiraterone/prednisone in patients with high-risk localized or locally advanced prostate cancer. II. To determine the safety and tolerability of neoadjuvant abiraterone/prednisone in patients with high-risk localized or locally advanced prostate cancer planning to undergo radical prostatectomy (RP). III. To assess time to biochemical recurrence following radical prostatectomy after 12 weeks of neoadjuvant abiraterone/prednisone IV. To assess prostate-specific antigen (PSA) response to neoadjuvant abiraterone/prednisone prior to RP. EXPLORATORY OBJECTIVES: I. To assess the diagnostic performances of multiparametric MRI (mpMRI) and hyperpolarized 13C MRI (HP13C MRI) for pathological response at the time of RP II. To investigate the association between early changes in intratumoral metabolism (HP 13C derived pyruvate-to-lactate conversion rate kPL) on neoadjuvant abiraterone with PSA nadir. III. To evaluate associations between baseline genomic and transcriptional features, changes in intratumoral kPL, and pathologic response at the time of radical prostatectomy. OUTLINE: Participants will receive 12 weeks of neoadjuvant abiraterone/prednisone. After completion of neoadjuvant therapy, participants will proceed to radical prostatectomy. Participants will be followed for up to 5 years every 3 months for the first year following RP, then every 6 months until death, biochemical recurrence or initiation of additional prostate cancer directed therapy.
Arms & interventions
- DrugAbiraterone acetate
Given orally
- DrugPrednisone
Given orally
- DrugHyperpolarized [1-13C] pyruvate (HP 13C)
Given IV
- ProcedureMagnetic Resonance Imaging (MRI)
Imaging procedure
- ProcedureNon-investigational radical prostatectomy (RP)
Planned, standard of care surgical procedure occurring outside of this study.
- ProcedureProstate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) PET/Computerized tomography (CT)
Imaging procedure
Outcome measures
Primary
Mean changes in intratumoral pyruvate-to-lactate conversion rate constant (kPL)
Mean changes in intratumoral kPL from baseline to 4 weeks will be reported. For participants with \>1 intraprostatic lesions detected on baseline scan, change in kPL will be calculated on using the lesion with the highest initial kPL.
Time frame: Up to 4 weeks
Secondary
Pathological response rate
Time frame: Up to 3 months
Proportion of participants with treatment-related adverse events (TRAE)
Time frame: Up to 3 months
Proportion of participants completing non-interventional radical prostatectomy (RP)
Time frame: Up to 8 weeks following completion of neoadjuvant treatment.
Median Time to Biochemical Recurrence
Time frame: Up to 5 years
Proportion of participants with a >=50% decline in PSA level from baseline (PSA50) response
Time frame: Up to 4 months
Proportion of participants with a >=90% decline in PSA level from baseline (PSA90) response
Time frame: Up to 4 months
Mean PSA nadir
Time frame: Up to 4 months
Eligibility criteria
Study locations (1)
University of California, San Francisco
San Francisco, California, 94143