Special MRI for Prostate Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ivan de Kouchkovsky, MD

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Hypertension, Heart failure, EKG abnormalities, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new MRI technique to predict treatment effectiveness for high-risk prostate cancer. Participants will receive two medications, abiraterone acetate (Zytiga) and prednisone, and undergo special MRI scans with an injection to track cancer changes. The goal is to determine if these scans can serve as an early signal of the cancer's response to treatment. Men with untreated, high-risk prostate cancer planning surgery might be suitable for this trial. As a Phase 2 trial, this research measures treatment effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in prostate cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop using 5-alpha reductase inhibitors at least 3 weeks before starting the trial. You also cannot use strong CYP3A4 inhibitors or inducers during the trial.

What prior data suggests that this MRI technique is safe for prostate cancer patients?

Research has shown that using abiraterone acetate with prednisone is generally safe for patients. In some studies, this combination has helped patients live longer. Serious side effects occurred less frequently in those taking abiraterone compared to standard treatments, with 64.1% of abiraterone users experiencing severe side effects. The most common issues reported were tiredness, high blood pressure, and low potassium levels.

Overall, while some risks exist, abiraterone and prednisone are usually well-tolerated. Those considering joining a trial should discuss any concerns with their doctor, who can provide specific advice based on individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it combines the use of abiraterone acetate and prednisone with a special imaging technique, hyperpolarized 13C-pyruvate MRI, to treat prostate cancer. This unique approach allows for detailed imaging of the prostate, which can help in better understanding how well the cancer is responding to the treatment in real-time. Unlike standard imaging methods, this technique provides more precise metabolic information, potentially leading to more tailored and effective treatment plans. Additionally, the combination of medications and advanced imaging could offer quicker insights into treatment effectiveness, potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants will receive a combination of abiraterone acetate and prednisone, alongside hyperpolarized 13C-pyruvate MRI scans. Studies have shown that abiraterone acetate with prednisone can significantly benefit patients with prostate cancer. Research indicates that this combination can extend the time patients live without their cancer worsening, with an average of 33 months without progression compared to 14.8 months for those not on this treatment. Additionally, over 64% of patients experienced a drop in their prostate-specific antigen (PSA) levels, an important indicator of cancer progression. This treatment has proven effective for patients both with and without prior chemotherapy, demonstrating its wide-ranging benefits. Overall, abiraterone with prednisone has been shown to help patients live longer and reduce cancer markers. ^{1 3 4 6 7}

Who Is on the Research Team?

Ivan de Kouchkovsky, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Men with high-risk, localized or locally advanced prostate cancer who haven't had treatment yet can join this trial. They'll be tested using a special type of MRI to see how well their cancer responds to a new therapy before having surgery.

Inclusion Criteria

Participant must agree to use a condom 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 pregnant woman while on study drug and for 8 weeks following the last dose of study drug

I have another cancer type, but it won't affect this trial's treatment.

My scans show no cancer spread far from the original site.

Exclusion Criteria

Patients unwilling or unable to undergo MR imaging, including patients with contraindications to MRI such as cardiac pacemakers or non-compatible intracranial vascular clips

Patients who cannot tolerate or have contra-indications to endorectal coil insertion

I have previously undergone treatment for prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive neoadjuvant abiraterone/prednisone for 12 weeks, with MRI scans at screening, cycle 2 day 1, and after completion of therapy

12 weeks

3 visits (in-person)

Radical Prostatectomy

Participants undergo planned, non-investigational radical prostatectomy within 7-56 days after last dose of neoadjuvant therapy

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 3 months for the first year, then every 6 months

Up to 5 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone acetate
• Non-investigational radical prostatectomy (RP)
• Prednisone

Trial Overview The study is testing if a special MRI scan called HP 13C MRI can show early on if the cancer treatment is working. Men in the trial will take Abiraterone and Prednisone before getting their prostates removed surgically.

How Is the Trial Designed?

Group I: Treatment (Abiraterone/Prednisone, Hyperpolarized (HP) 13C Pyruvate) Experimental Treatment 6 Interventions

Neoadjuvant abiraterone (1000mg) will be administered for three 28-day cycles, in conjunction with 5mg of prednisone. Participants will undergo a paired multi-parametric/hyperpolarized MRI of the prostate at screening, cycle 2 day 1, and after completion of neoadjuvant therapy. With each scan, a hyperpolarized 13C-pyruvate injection will be administered. A planned, non-investigational RP will be completed within 7-56 days after last dose/discontinuation of neoadjuvant study drug. Participants will be followed up until death, withdrawal of consent, or end of study, whichever occurs first.

Abiraterone acetate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Ivan de Kouchkovsky, MD

Lead Sponsor

Trials

3

Recruited

190+

Published Research Related to This Trial

MRI is becoming increasingly important for diagnosing and monitoring prostate cancer, with ongoing research aimed at identifying specific imaging characteristics that enhance its effectiveness.

The article discusses the Prostate Imaging Reporting and Data System (PI-RADS), a standardized scoring and reporting system that helps radiologists evaluate prostate MRI results, particularly for patients with varying biopsy histories and PSA levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging for prostate cancer: what the urologist needs to know. Kiechle, J., Pahwa, S., Gulani, V., et al.[2017]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Switching from prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate resulted in a median progression-free survival (PFS) of 10.35 months, compared to 8.94 months on prednisone, indicating a potential benefit of this switch.

The effectiveness of the switch was particularly notable in patients with longer hormone sensitivity duration, lower PSA levels at the time of switch, and shorter time to PSA progression, suggesting that these factors can help predict better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer. Fenioux, C., Louvet, C., Charton, E., et al.[2019]

Magnetic resonance imaging (MRI) has a significant diagnostic performance for detecting prostate cancer in patients with prior negative biopsies and elevated PSA levels, with a mean detection rate of 37.5% across 14 studies involving 698 patients.

MRI combined with magnetic resonance spectroscopy imaging (MRSI) shows the highest accuracy, achieving a pooled sensitivity of 91% and specificity of 73%, indicating it is a valuable tool for targeting prostate cancer in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of magnetic resonance imaging in the detection of prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen levels: a meta-analysis. Zhang, ZX., Yang, J., Zhang, CZ., et al.[2022]

Dynamic contrast-enhanced MRI at both 1.5 T and 3 T can effectively differentiate prostate cancer from normal prostate tissue, with prostate cancer showing significantly higher plasma flow and shorter mean transit time compared to normal tissue.

At 3 T, the diagnostic accuracy for distinguishing prostate cancer from prostatitis is improved, with sensitivity and specificity of 89% and 73%, respectively, compared to 46% and 88% at 1.5 T.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interscanner comparison of dynamic contrast-enhanced MRI in prostate cancer: 1.5 versus 3 T MRI. Sertdemir, M., Schoenberg, SO., Sourbron, S., et al.[2013]

MRI is the preferred imaging method for evaluating prostate cancer, helping to guide targeted biopsies, localize and stage cancer, and detect any residual or recurrent disease after treatment.

Advanced MRI techniques like proton MR spectroscopic imaging, diffusion-weighted imaging, and contrast-enhanced MRI enhance the accuracy of prostate cancer detection and characterization, making them valuable tools in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR imaging of the prostate in clinical practice. Mazaheri, Y., Shukla-Dave, A., Muellner, A., et al.[2022]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

In a study of 131 patients with high-risk, nonmetastatic, castration-resistant prostate cancer, treatment with abiraterone acetate and prednisone resulted in an impressive 86.9% of patients achieving a 50% or greater reduction in prostate-specific antigen (PSA) levels, indicating strong efficacy.

The treatment also showed promising secondary outcomes, with a median time to PSA progression of 28.7 months, while safety was generally acceptable, although 96.2% of patients experienced adverse events, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer. Ryan, CJ., Crawford, ED., Shore, ND., et al.[2021]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

The updated PI-RADS version 2.1 emphasizes the importance of diffusion-weighted imaging in the transition zone of the prostate, which may enhance the accuracy of prostate cancer diagnosis.

A mandatory high b-value of at least 1400 s/mm2 is now required for imaging, aiming to reduce variability in interpretation and improve detection rates, although further clinical studies are needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI-RADS 2.1 - Image Interpretation: The Most Important Updates and Their Clinical Implications. Beyer, T., Schlemmer, HP., Weber, MA., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33826036/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ... The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group ( ...

3. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.367

Real-world discontinuation and efficacy data of abiraterone ... Background: Data from STAMPEDE trial confirmed Overall survival benefit for patients with high-risk localized or locally advanced prostate ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9058899/

Real-world experience of abiraterone acetate plus prednisone ... A PSA response (≥50%) during abiraterone treatment was achieved by 272 patients (64.2% of 424 patients with available information; 59.9% of all ...

5. zytigahcp.com zytigahcp.com/efficacy-and-safety/

Metastatic High-Risk CSPC LATITUDE Study A major efficacy outcome was overall survival. The pre-specified interim analysis after 406 deaths showed a statistically significant improvement in OS in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8105236/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

7. mdpi.com mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ... More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent ...