Genomics in Michigan to AdJust Outcomes in Prostate canceR (G-MAJOR) for Men With Newly Diagnosed Favorable Risk Prostate Cancer

• ClinicalTrials.gov Identifier: NCT04396808
• Recruitment Status: Recruiting
• First Posted: May 21, 2020
• Last Update Posted: November 14, 2022
• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Institutes of Health (NIH); Myrexis Inc.; Veracyte, Inc.; MDx Health
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

Study Description

Brief Summary:

This study seeks to determine the clinical impact of Gene Expression Classifier (GEC) testing in prostate cancer care while also developing a pragmatic approach for improved GEC clinical use and future study.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Device: Decipher; Device: Prolaris; Device: Oncotype Dx Genomic Prostate Score (GPS); Other: Standard of care (askMUSIC score)	Not Applicable

Detailed Description:

All patients in this study have received or will receive a score from the Michigan Urological Surgery Improvement Collaborative's Cancer of the Prostate Risk Assessment (askMUSIC) scoring system, at the time of enrollment. AskMUSIC is a risk calculator based on standard clinical and pathologic variables and is generally included as part of routine clinical care. The variables used in the risk calculator are prostate-specific antigen (PSA), Gleason score, number of positive core biopsies, number of negative core biopsies, and clinical stage.

Patients will be randomized to either an intervention arm or a control arm. In the control arm, the treating provider will review the askMUSIC score with the patient. In the intervention arm, the treating provider will review the askMUSIC and the GEC score with the patient. Biopsies obtained during the course of standard clinical care will be analyzed using one of the following GECs: Decipher, Prolaris or Oncotype Dx Genomic Prostate Score. No additional biopsies will be obtained as part of this study.

After reviewing the results, patients and their treating physicians will decide on a management strategy.

Long-term follow-up will be tracked through the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 900 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: 1:1 cluster-crossover in 3 month blocks
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Genomics in Michigan to AdJust Outcomes in Prostate canceR (G-MAJOR): A Randomized Multi-center Study for Men With Newly Diagnosed Favorable Risk Prostate Cancer
• Actual Study Start Date: November 5, 2020
• Estimated Primary Completion Date: November 2023
• Estimated Study Completion Date: November 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard of care (no pre-treatment genomics testing); Provider will discuss askMUSIC results with patient prior to deciding on a management strategy (standard of care).	Other: Standard of care (askMUSIC score); AskMUSIC is a risk calculator based on standard clinical and pathologic variables (https://ask.musicurology.com/) and is generally included as part of routine clinical care.; Other Name: askMUSIC score
Active Comparator: Standard of care + pre-treatment genomics testing; Provider will discuss askMUSIC and Gene Expression Classifier (GEC) results with patient prior to deciding on a cancer management strategy. Patients' biopsy tissue will be analyzed using one of the following GECs: Decipher, Prolaris or Oncotype Dx.	Device: Decipher; The Decipher test (GenomeDx Biosciences) is a genomic test that will be performed on prostate biopsy tissue. Results will be provided to the patient and physician prior to making a treatment decision.; Other Name: Decipher Prostate Cancer Classifier; Device: Prolaris; The Prolaris test (Myriad Genetics, Inc.) is a genomic test that will be performed on prostate biopsy tissue. Results will be provided to the patient and physician prior to making a treatment decision.; Other Name: Prolaris Prostate Cancer Test; Device: Oncotype Dx Genomic Prostate Score (GPS); The Oncotype Dx GPS test (Exact Sciences corp.) is a genomic test that will be performed on prostate biopsy tissue. Results will be provided to the patient and physician prior to making a treatment decision.; Other: Standard of care (askMUSIC score); AskMUSIC is a risk calculator based on standard clinical and pathologic variables (https://ask.musicurology.com/) and is generally included as part of routine clinical care.; Other Name: askMUSIC score

Outcome Measures

Primary Outcome Measures :

1. Binomial proportion of men on active surveillance without treatment [ Time Frame: At 2 years ]

Secondary Outcome Measures :

1. Occurence of grade reclassification [ Time Frame: At 2 years ]
   Grade reclassification defined as an increase in grade group on surveillance biopsy (GG=1 to GG≥2 or GG=2 to GG≥3) for patients managed on active surveillance
2. Rate of indolent pathology [ Time Frame: At time of prostatectomy (for patients who undergo procedure), up to 2 years ]
   To determine the impact of GEC testing on the rate of potentially unnecessary surgery, as defined by indolent pathology at prostatectomy (GG1 and stage pT2).
3. Mean score per arm of patient reported urinary function questionnaire [ Time Frame: At 2 years ]
   Assessed by patient reported Expanded Prostate Cancer Index (EPIC) Urinary Incontinence Domain (UIN) questionnaire. Response options form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better quality of life (QOL).
4. Proportion of patients with changes from baseline in urinary function exceeding Minimal Important Differences (MID). [ Time Frame: Baseline to 12 months and 2 years ]
   Assessed by patient reported EPIC UIN questionnaire. For this measure, MID = 9 points.
5. Mean score per arm of patient reported sexual function questionnaire [ Time Frame: At 2 years ]
   Assessed by patient reported Expanded Prostate Cancer Index (EPIC) sexual domain questionnaire. Response options form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better QOL.
6. Proportion of patients with changes from baseline in sexual function exceeding Minimal Important Differences (MID). [ Time Frame: Baseline to 12 months and 2 years ]
   Assessed by patient reported EPIC sexual function questionnaire. For this measure, MID = 11 points.
7. Time to biochemical recurrence (BCR) [ Time Frame: From time of radical therapy until the event or the last measured follow-up, up to 2 years ]
   Time from treatment PSA >= 0.2 ng/mL for patients undergoing surgery (with PSA at least 5 weeks after surgery) and nadir plus 2.0 ng/mL for patients undergoing radiotherapy.
8. Time to distant metastases [ Time Frame: From time of radical therapy until the event or the last measured follow-up, up to 2 years ]
   Assessed by CT, MRI, bone scan, and/or PET scan
9. Mean score per arm of health-related quality of life (HRQOL) [ Time Frame: At 2 years ]
   Assessed by patient reported Expanded Prostate Cancer Index Composite short form (EPIC-26). EPIC-26 encompasses 5 domains (Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal). Response options for each of 26 items form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
10. Rate of adverse pathology at prostatectomy [ Time Frame: At time of prostatectomy, up to 5 years from enrollment ]
    To determine the performance of GEC testing in predicting adverse pathology, defined as GG≥3 and/or ≥pT3 disease.
11. Rate of biochemical recurrence [ Time Frame: Up to 5 years following treatment ]
    To determine the performance of GEC testing in predicting biochemical recurrence, defined as PSA >= 0.2 ng/mL for patients undergoing surgery (with PSA at least 5 weeks after surgery) and nadir plus 2.0 ng/mL for patients undergoing radiotherapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Prostate cancer patients who have undergone diagnostic prostate biopsy in the past 9 months.
• Prostate biopsy tumor tissue (FFPR block) available for processing
• Age 18 years or older
• PSA <20 ng/ml
• Grade Group (GG) 1 cancer with > 2 biopsy cores involved with cancer OR GG2 cancer
• Ability to understand and the willingness to sign a written informed consent. A subject's legally acceptable representative may sign the consent form.

Exclusion Criteria:

• Clinical (on digital rectal exam) or radiographic evidence (if MRI performed) of T3 disease
• Nodal or metastatic prostate cancer (if staging imaging performed)
• Prior prostate cancer treatment, including prostatectomy, radiation therapy, or hormone therapy.
• Prior prostate gene expression classier testing

Contacts and Locations

Contacts

Contact: G-Major Study; 734-764-4060; gmajorstudy@med.umich.edu

Locations

United States, Michigan

University of Michigan Rogel Cancer Center; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: G-Major Study 734-764-4060 gmajorstudy@med.umich.edu

Principal Investigator: Todd Morgan, M.D.

Sub-Investigator: Daniel Spratt, M.D.

Henry Ford Health System; Recruiting

Detroit, Michigan, United States, 48202

Principal Investigator: Craig Rogers, MD

Sherwood Medical Center; Recruiting

Detroit, Michigan, United States, 48221

Principal Investigator: Conrad Maitland, MD

Western Michigan Urological Associates; Recruiting

Holland, Michigan, United States, 49423

Principal Investigator: John Ludlow, MD

Sponsors and Collaborators

University of Michigan Rogel Cancer Center

National Institutes of Health (NIH)

Myrexis Inc.

Veracyte, Inc.

MDx Health

Investigators

• Principal Investigator: Todd Morgan, M.D.; University of Michigan
• Principal Investigator: Daniel Spratt, M.D.; University of Michigan

More Information

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT04396808
• Other Study ID Numbers: UMCC 2019.132; HUM00173277 ( Other Identifier: University of Michigan )
• First Posted: May 21, 2020
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University of Michigan Rogel Cancer Center:

Biomarkers; Active surveillance; Gene Expression Classifier

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases