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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the drug Abiraterone acetate (Zytiga) in combination with prednisone for prostate cancer?

Research shows that Abiraterone acetate (Zytiga) combined with prednisone significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer, as demonstrated in clinical trials where it outperformed placebo. ^{1 2 3 4 5}

Is abiraterone acetate safe for humans?

Abiraterone acetate, used with prednisone, is generally considered safe for treating metastatic castration-resistant prostate cancer, though it can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. These side effects were relatively low in frequency during clinical trials. ^{1 2 3 6 7}

How is the drug Abiraterone acetate with Prednisone unique for prostate cancer treatment?

Abiraterone acetate with Prednisone is unique because it works by blocking the production of androgens (male hormones) that can fuel prostate cancer growth, offering a different approach compared to traditional chemotherapy. This combination is often used when the cancer has spread and other treatments are no longer effective. ^{8 9 10 11 12}

Research Team

Ivan de Kouchkovsky, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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 prostate cancer diagnosis was confirmed through a biopsy, and the sample is available for further testing.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2018]

2. Sweden 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. [2017]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

4. United States 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. [2021]

5. England 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. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. Germany 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Interscanner comparison of dynamic contrast-enhanced MRI in prostate cancer: 1.5 versus 3 T MRI. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

PI-RADS 2.1 - Image Interpretation: The Most Important Updates and Their Clinical Implications. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

MR imaging of the prostate in clinical practice. [2022]

11. Italy pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging for prostate cancer: what the urologist needs to know. [2017]

12. United States 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. [2022]