GPS Assay + MRI for Prostate Cancer

(MAGIC Trial)

Recruiting at 1 trial location

Overseen By Daniel Moreira

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Life expectancy <10 years, MRI contraindication, others

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

Compensation: Varies

Number of Visits: 1

222 Participants Needed

Trial Summary

What is the purpose of this trial?

The overarching goal is to prospectively recruit men considering active surveillance for treatment in the MAGIC (MRI And GPS Informing Choices for prostate cancer treatment) Cohort to provide meaningful data on active surveillance in Blacks and in men served in safety net hospitals. Recent studies highlight significant promise for multi-parametric magnetic resonance imaging of the prostate (MRI) and Genomic Prostate Score assay (GPS) as tools to help risk stratify men on active surveillance to identify men likely to harbor undetected aggressive disease in their prostate. Given the risk data provided by these modalities and the low adherence with monitoring common in men served in public hospitals, both tools may improve safety via improved patient selection and patient adherence with monitoring. The downside is that excessive testing may lead to too many false positives and unnecessary treatment. Two hundred men with very low to intermediate risk prostate cancer were randomized into the 2-arm ENACT Clinical trial from 2016-2019 to study the impact of the GPS assay on treatment choice. Overall, 104 men received GPS assay and 96 controls did not receive the assay (a confirmatory test) right after being newly diagnosed with favorable risk prostate cancer. For Aim 1, 222 men will be recruited into the MRI And GPS Informing Choices for prostate cancer treatment (MAGIC) study and they will be given the GPS assay and multi-parametric MRI of the prostate to provide personalized risk data for having aggressive tumors in their prostate. Between the ENACT and MAGIC study, there will be 3 groups of men who will have received both GPS \& MRI, GPS alone, or neither test and can compare the impact of having 0,1 or 2 confirmatory tests on patient's adherence to active surveillance monitoring protocols over 18 months. The analyses will elucidate whether 1 or 2 tests are needed to improve adherence to monitoring. Monitoring is vital for detecting tumor progression early and avoiding cancer metastasis and death. In Aim 2, the MAGIC study cohort will be leveraged to determine the accuracy of the Genomic Prostate Score assay and the prostate imaging- reporting and data system (PIRADS) score from the MRI in predicting which tumors will progress in 18 months. Progression is defined as increased Gleason grade group (GG) or change in prostate digital rectal examination findings. This serves two purposes. It will allow doctors and patients to categorize the patient as safe or risky for active surveillance. Secondly, it will allow doctors to identify which men on active surveillance need to be followed with annual prostate biopsies and which men can have their biopsies deferred for 3-5 years to reduce the number of prostate biopsies and their morbidities. Lastly in Aim 3, the participants will rank the importance of these tests among a multitude of clinical, social, financial and interpersonal influences on their cancer treatment choice. By tallying the patient rankings, one can identify the most critical decision making factors that can be used to encourage increased selection of active surveillance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment GPS Assay + MRI for Prostate Cancer?

Research shows that the Genomic Prostate Score (GPS) assay, when combined with multi-parametric MRI, provides valuable information for assessing the risk of adverse pathology in prostate cancer. This combination helps in better predicting the severity of prostate cancer, which can guide treatment decisions. ^{1 2 3 4 5}

Is the GPS Assay + MRI safe for humans?

The research articles do not provide specific safety data for the GPS Assay + MRI, but they focus on its use in assessing prostate cancer risk and pathology. Generally, both genomic tests and MRI are considered safe procedures in medical practice. ^{1 2 3 6 7}

How does the GPS Assay + MRI treatment for prostate cancer differ from other treatments?

The GPS Assay + MRI treatment is unique because it combines a 17-gene genomic test with advanced imaging (MRI) to better assess the risk and guide treatment decisions for prostate cancer. This approach helps in predicting adverse pathology and improving risk stratification, which is not typically achieved with standard treatments. ^{1 2 4 8 9}

Eligibility Criteria

The MAGIC trial is for men aged 40-76 with very low to favorable intermediate risk prostate cancer, diagnosed within the last 3 months and considering active surveillance. It excludes those who can't have an MRI or transrectal ultrasound, can't complete surveys, or have less than a decade expected lifespan.

Inclusion Criteria

I am open to monitoring my condition without immediate treatment.

Participants must be diagnosed within 3 months prior to study enrollment

My prostate cancer is classified from very low to favorable intermediate risk.

Exclusion Criteria

Participants with a contraindication to magnetic resonance imaging (MRI)

Participants unable to complete standardized surveys

I cannot have a transrectal ultrasound due to lack of rectal access.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment

Participants undergo Genomic Prostate Score assay and multi-parametric MRI of the prostate to provide personalized risk data

4 weeks

1 visit (in-person)

Active Surveillance Monitoring

Participants who choose active surveillance are monitored with PSA tests, digital rectal exams, and prostate biopsies

18 months

Regular visits as per clinical routine

Follow-up

Participants are monitored for safety and effectiveness after the active surveillance period

6 months

Treatment Details

Interventions

• Genomic Prostate Score assay
• Multi-parametric magnetic resonance imaging study of the prostate

Trial Overview This study tests if using Genomic Prostate Score (GPS) assays and multi-parametric MRIs helps better identify aggressive prostate tumors in men opting for active surveillance. The goal is to see if these tools improve patient adherence to monitoring protocols over 18 months.

Participant Groups

Group I: Genomic Prostate Score assay and multi-parametric MRI of the prostate Experimental Treatment 1 Intervention

Men with newly diagnosed NCCN very low to favorable intermediate risk prostate cancer will be enrolled at their post biopsy urologist visit. Once enrolled, participants will have their prostate tissue sent off for their Genomic Prostate Score assay and men will undergo a prostate MRI to evaluate for potentially missed clinically significant prostate cancer. In a subsequent urologist visit, participants will choose their treatment choice. Men who choose active surveillance for their primary treatment choice will be monitored per clinical routine by PSA, digital rectal exam, and active surveillance prostate biopsy in 12-18 months. After month 6, men will be followed through their electronic medical records system to track adherence to their 12-18 month active surveillance prostate biopsy.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study of 100 men with low and intermediate risk prostate cancer, there was a significant association between the Genomic Prostate Score (GPS) and multi-parametric MRI (mpMRI) findings, indicating that both tests provide valuable but different insights into cancer characteristics.

While GPS results varied significantly across different mpMRI categories, a wide range of GPS values was observed within each category, suggesting that mpMRI and genomic profiling may complement each other rather than replace one another in clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa). Leapman, MS., Westphalen, AC., Ameli, N., et al.[2018]

The 17-gene Oncotype DX® Genomic Prostate Score™ assay is a significant independent predictor of adverse pathology findings in men with very low, low, or intermediate risk prostate cancer, even when diagnosed through advanced imaging techniques like multiparametric MRI.

In a study of 134 men, the prostate score assay remained a strong predictor of adverse pathology after adjusting for other clinical factors, suggesting it can enhance risk stratification and treatment decisions for prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 17-Gene Genomic Prostate Score Assay Provides Independent Information on Adverse Pathology in the Setting of Combined Multiparametric Magnetic Resonance Imaging Fusion Targeted and Systematic Prostate Biopsy. Salmasi, A., Said, J., Shindel, AW., et al.[2019]

In a study of 131 patients, the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) demonstrated moderate interobserver agreement among radiologists, with intraclass correlation coefficients (ICC) ranging from 0.67 to 0.74 for different lesion types.

Despite the moderate agreement, PI-RADS v2 effectively predicted the likelihood of intermediate- and high-grade prostate cancers, with positive predictive values (PPV) increasing significantly from 0% for category 2 to 87% for category 5, indicating its utility in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): Interobserver Agreement and Positive Predictive Value for Localization of Intermediate- and High-Grade Prostate Cancers on Multiparametric Magnetic Resonance Imaging. Chen, F., Cen, S., Palmer, S.[2018]

In a study of 262 patients, specific magnetic resonance imaging features, particularly signal abnormalities and volume measurements, were effective in diagnosing clinically significant prostate cancers (csPCa), with the best models achieving an area under the curve (AUC) of up to 0.840.

The diagnostic performance improved when combining signal-related variables with factors like extracapsular extension and PSA density, indicating that a tailored approach based on the definition of csPCa can enhance diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value and relative weight of sequence-specific magnetic resonance features in characterizing clinically significant prostate cancers. Rouvière, O., Dagonneau, T., Cros, F., et al.[2018]

In a study of 79 patients who underwent MRI-guided biopsy and radical prostatectomy, specific MRI features such as a PI-RADS score of 5 and suspicion of extraprostatic extension were significantly associated with shorter recurrence-free survival (RFS) after surgery.

Preoperative p53 immunohistochemistry stain intensity also correlated with RFS, suggesting that both imaging characteristics and molecular markers can help predict the risk of biochemical recurrence in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Features of Biochemical Recurrence of Prostate Cancer Following Radical Prostatectomy Based on Multiparametric MRI and Immunohistochemistry Analysis of MRI-guided Biopsy Specimens. Harmon, SA., Gesztes, W., Young, D., et al.[2022]

In a study of 176 patients with suspicious findings on prostate mpMRI, the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) showed a positive predictive value (PPV) of 70.2% for detecting high-grade prostate cancer (Gleason score ≥7) in category 5 lesions, indicating its effectiveness in identifying serious cases.

The PPV was even higher at 88% for category 5 lesions located in the peripheral zone, demonstrating that both the PI-RADS category and the lesion's location significantly influence the likelihood of detecting clinically significant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in patients with a solitary PI-RADS v2-scored lesion. Syed, JS., Nguyen, KA., Nawaf, CB., et al.[2018]

The 17-gene Oncotype DX Genomic Prostate Score (GPS) test was evaluated in a study of 432 men with low-risk prostate cancer under active surveillance, but it did not significantly improve the prediction of adverse pathology (AP) compared to traditional clinical variables like Gleason Grade Group (GG) and prostate-specific antigen density (PSAD).

While GPS was associated with AP when adjusted for GG, this association became non-significant when PSAD was also considered, indicating that GPS may not provide additional predictive value in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

17-Gene Genomic Prostate Score Test Results in the Canary Prostate Active Surveillance Study (PASS) Cohort. Lin, DW., Zheng, Y., McKenney, JK., et al.[2022]

The Genomic Prostate Score (GPS) assay is a strong independent predictor of biochemical recurrence (BCR), distant metastases (DM), and prostate-specific death (PCD) in patients with unfavorable intermediate risk prostate cancer, based on an analysis of 299 patients from two studies.

Patients with a GPS score greater than 40 have outcomes indicative of high-risk disease, suggesting they may require more aggressive treatment options, while those with a score of 40 or lower have outcomes similar to favorable intermediate risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 17-Gene Genomic Prostate Score Test as a Predictor of Outcomes in Men with Unfavorable Intermediate Risk Prostate Cancer. Cullen, J., Kuo, HC., Shan, J., et al.[2022]

In a study of 215 men on active surveillance for prostate cancer, a higher Oncotype Dx® Genomic Prostate Score (GPS) was linked to an increased risk of adverse pathology findings after radical prostatectomy, indicating its potential as a predictive tool for disease progression.

The GPS was also associated with a higher risk of biochemical recurrence post-surgery, suggesting that it may help identify patients who need closer monitoring or more aggressive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 17-Gene Genomic Prostate Score as a Predictor of Adverse Pathology in Men on Active Surveillance. Kornberg, Z., Cooperberg, MR., Cowan, JE., et al.[2020]

References

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

Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa). [2018]

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

A 17-Gene Genomic Prostate Score Assay Provides Independent Information on Adverse Pathology in the Setting of Combined Multiparametric Magnetic Resonance Imaging Fusion Targeted and Systematic Prostate Biopsy. [2019]

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

Application of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): Interobserver Agreement and Positive Predictive Value for Localization of Intermediate- and High-Grade Prostate Cancers on Multiparametric Magnetic Resonance Imaging. [2018]

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

Diagnostic value and relative weight of sequence-specific magnetic resonance features in characterizing clinically significant prostate cancers. [2018]

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

Prognostic Features of Biochemical Recurrence of Prostate Cancer Following Radical Prostatectomy Based on Multiparametric MRI and Immunohistochemistry Analysis of MRI-guided Biopsy Specimens. [2022]

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

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion-targeted biopsy in patients with a solitary PI-RADS v2-scored lesion. [2018]

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

17-Gene Genomic Prostate Score Test Results in the Canary Prostate Active Surveillance Study (PASS) Cohort. [2022]

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

The 17-Gene Genomic Prostate Score Test as a Predictor of Outcomes in Men with Unfavorable Intermediate Risk Prostate Cancer. [2022]

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

A 17-Gene Genomic Prostate Score as a Predictor of Adverse Pathology in Men on Active Surveillance. [2020]