Hyperpolarized (HP) 13C Pyruvate Magnetic Resonance Imaging (MRI) for Response Monitoring to Neoadjuvant Abiraterone

Prostate Cancer Clinical Trial

Official title:

Hyperpolarized (HP) 13C Pyruvate Magnetic Resonance Imaging (MRI) as a Response Monitoring Tool in Patients With High-Risk Prostate Cancer Receiving Neoadjuvant Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06384222
• Other study ID #: 235513
• Secondary ID: NCI-2024-03418
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2024
• Est. completion date: July 31, 2027

Study information

• Verified date: June 2024
• Source: University of California, San Francisco
• Contact: Maya Aslam
• Phone: (415) 514-8987
• Email: Maya.Aslam[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 PSMA PET, 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: July 31, 2027
• Est. primary completion date: July 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Greater than or equal to 18 years of age

2. Histologically confirmed adenocarcinoma of the prostate with archival biopsy tissue available for genomic profiling.

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 1.

7. Participant must agree to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or must agree to use a condom if having sex with a woman who is pregnant while on study drug and for 8 weeks following the last dose of study drug. Participant must also agree not to donate sperm during the study and for 8 weeks after receiving the last dose of study drug.

8. 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).

9. Ability to understand and the willingness to sign a written informed consent document.

10. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

11. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

12. 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.

13. 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.

14. 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 exclusion criteria will not apply.

3. Participants with contra-indications to injection of gadolinium contrast; for example, participants with prior documented allergy or those with inadequate renal function.

4. Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.

5. Poorly controlled hypertension, with blood pressure at study entry >160 mmHg systolic or >100 mmHg diastolic.

6. Congestive heart failure with New York Heart Association (NYHA) status >=2.

7. A history of clinically significant EKG abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction within 6 months of study entry.

8. Has received prior prostate cancer therapy.

a. Prior 5-alpha reductase inhibitors (e.g. finasteride, dutasteride) allowed if discontinued at least 3 weeks prior to first dose.

9. Is currently receiving any other investigational agent(s) or has participated in a study of an investigational product and received study treatment or used an investigational device within 2 weeks of the first dose of treatment.

10. Concurrent use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital).

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone acetate
Given orally
• Prednisone
Given orally
• Hyperpolarized [1-13C] pyruvate (HP 13C)
Given IV

Procedure:
• Magnetic Resonance Imaging (MRI)
Imaging procedure
• Non-investigational radical prostatectomy (RP)
Planned, standard of care surgical procedure occurring outside of this study.
• Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) PET/Computerized tomography (CT)
Imaging procedure

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Ivan de Kouchkovsky, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 4 weeks
Secondary	Pathological response rate	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.	Up to 3 months
Secondary	Proportion of participants with treatment-related adverse events (TRAE)	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.	Up to 3 months
Secondary	Proportion of participants completing non-interventional radical prostatectomy (RP)	Proportion of patients successfully undergoing planned, non-interventional RP following neoadjuvant therapy will be reported.	Up to 8 weeks following completion of neoadjuvant treatment.
Secondary	Median Time to Biochemical Recurrence	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.	Up to 5 years
Secondary	Proportion of participants with a >=50% decline in PSA level from baseline (PSA50) response	Proportion of patients with a PSA50 response defined as a >=50% decline in PSA level from baseline during neoadjuvant treatment will be reported.	Up to 4 months
Secondary	Proportion of participants with a >=90% decline in PSA level from baseline (PSA90) response	Proportion of patients with a PSA90 response defined as a >=90% decline in PSA level from baseline during neoadjuvant treatment will be reported.	Up to 4 months
Secondary	Mean PSA nadir	The mean PSA nadir for participants while on neoadjuvant therapy will be reported.	Up to 4 months