High Risk Prostate Carcinoma, Prostate Cancer
Conditions
Brief 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.
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
Sponsors
Ivan de Kouchkovsky, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Greater than or equal to 18 years of age 2. Histologically confirmed adenocarcinoma of the prostate with archival biopsy tissue (collected within 12 months of cycle 1 day 1 of treatment) available for genomic profiling. a. Tumor tissue does not need to be retrieved but rather identified and available upon later request for future pathologic review and possible correlative studies. 3. High-risk disease defined as meeting 1 or more of the 3 following criteria: 1. Gleason grade group \>=4; or 2. Pelvic node involvement by conventional imaging or PSMA PET imaging (cN1); or 3. Tumor stage T3 or higher (i.e. tumor extension outside of the prostate, or spread to tissues near the prostate other than the seminal vesicles, such as the bladder or wall of the pelvis) as determined by conventional imaging (including prostate MRI), transrectal ultrasound or PSMA PET imaging. 4. No evidence of distant metastatic disease as determined by PSMA PET/CT or PET/MR. Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. 5. Participants must be planning to undergo radical prostatectomy (RP) with or without pelvic lymph node dissection and considered surgically resectable by urologic evaluation at the time of study entry. Adjuvant therapy following RP will be allowed per treating provider discretion. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 7. Demonstrates adequate organ function as defined below: 1. Absolute neutrophil count (ANC) \>=1,500/microliter (mcL). 2. Platelets \>=100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start. 3. Total bilirubin within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits. 4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \<=3 X institutional upper limit of normal. 5. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<=3 X institutional upper limit of normal. 6. Estimated creatinine clearance \>=40 mL/min (by the Cockcroft Gault equation). 8. Ability to understand and the willingness to sign a written informed consent document. 9. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. 10. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. 11. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. 12. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. 13. Abiraterone may cause fetal harm when administered to a pregnant woman. The effects of hyperpolarized \[1-13C\]pyruvate on the developing human fetus are unknown. For this reason, men treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation and for 8 weeks after last administration of study treatment.
Exclusion criteria
1. Participants unwilling or unable to undergo MR imaging, including patients with contraindications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips. 2. Participants who cannot tolerate or have contra-indications to endorectal coil insertion; for example, patients with a prior abdominoperineal resection of the rectum or latex allergy. The use of an endorectal coil may be waived at the discretion of the Principal Investigator upon review of available imaging with radiology, in which case this
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean changes in intratumoral pyruvate-to-lactate conversion rate constant (kPL) | Up to 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological response rate | Up to 3 months | Pathological response rate is defined as the rate of combined pathological complete response (pCR) or minimal residual disease (MRD) at radical prostatectomy (RP). The point estimate and 95% confidence intervals will be reported. A pCR is defined as the absence of tumor on the gross specimen o MRD is defined as residual tumors with cross-sectional diameter of \<=0.5cm. |
| Proportion of participants with treatment-related adverse events (TRAE) | Up to 3 months | Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria. Proportion of participants reporting treatment-related adverse events will be reported. |
| Proportion of participants completing non-interventional radical prostatectomy (RP) | Up to 8 weeks following completion of neoadjuvant treatment. | Proportion of patients successfully undergoing planned, non-interventional RP following neoadjuvant therapy will be reported. |
| Median Time to Biochemical Recurrence | Up to 5 years | The Kaplan-Meier method will be used to estimate the median time to biochemical recurrence (along with 95% confidence intervals). Biochemical recurrence will be defined as a serum PSA \>=0.2 ng/mL confirmed on two separate occasions (with time of biochemical recurrence defined as the date of the first serum PSA \>=0.2 ng/mL). Participants deceased or initiated on a prostate cancer (PC)-directed therapy prior to biochemical recurrence will be censored at the time of death or initiation of PC-directed therapy. Similarly, participants removed from the trial prior to biochemical recurrence will be censored at the time of study removal. |
| Proportion of participants with a >=50% decline in PSA level from baseline (PSA50) response | Up to 4 months | Proportion of patients with a PSA50 response defined as a \>=50% decline in PSA level from baseline during neoadjuvant treatment will be reported. |
| Proportion of participants with a >=90% decline in PSA level from baseline (PSA90) response | Up to 4 months | Proportion of patients with a PSA90 response defined as a \>=90% decline in PSA level from baseline during neoadjuvant treatment will be reported. |
| Mean PSA nadir | Up to 4 months | The mean PSA nadir for participants while on neoadjuvant therapy will be reported. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORIvan de Kouchkovsky, MD
University of California, San Francisco
Outcome results
None listed