G-MINOR: Genomics in Michigan Impacting Observation or Radiation

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02783950
• Collaborator: Michigan Urological Surgery Improvement Collaborative (MUSIC) (Other), GenomeDx Biosciences Corp (Industry)
• Enrollment: 356
• Locations: 13
• Arms: 2
• Anticipated Duration (Months): 90.4
• Patients Per Site: 27.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To determine the impact of Decipher test results on adjuvant treatment decisions of high-risk post-RP patients with undetectable post-op prostate specific antigen (PSA) compared to clinical factors alone.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Other: Decipher Prostate Cancer Classifier	N/A

Detailed Description

This prospective, randomized trial will compare the receipt of adjuvant therapy for high-risk radical prostatectomy (RP) patients who undergo Decipher testing to those who do not. 350 subjects from within the statewide Michigan Urological Surgery Improvement Collaborative (MUSIC) will be randomized to either a Genomic Classifier (Decipher) or Usual-Care-Based (UC) strategy for a period of three months. If enrolled during the Genomic Classifier period, both subjects and their treating physician will be provided Decipher results and CAPRA-S scores. In the UC periods, CAPRA-S scores but not Decipher results will be provided.

The enrollment goal, initially and throughout the study, was to enroll 350 evaluable patients. During the study, the target accrual goal was raised to 550 patients to allow more flexibility among sites to achieve the enrollment goal of 350 evaluable patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 356 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Genomics in Michigan Impacting Observation or Radiation (G-MINOR)
• Actual Study Start Date: Jan 17, 2017
• Actual Primary Completion Date: Jan 1, 2020
• Anticipated Study Completion Date: Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: GC (Decipher) Arm If enrolled during the Genomic Classifier (GC) period, both subjects and their treating physician will be provided GC (Decipher Prostate Cancer Classifier from GenomeDx) and CAPRA-S scores following prostatectomy.	Other: Decipher Prostate Cancer Classifier; The Decipher test (GenomeDx Biosciences, San Diego, CA) is a genomic test that predicts high grade disease, the probability of metastasis and prostate cancer-specific mortality for men with prostate cancer.; Other Names: Decipher Post-Op
No Intervention: Usual-Care-Based (UC) Arm If enrolled during the UC period, only the CAPRA-S results will be provided.

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Receive Adjuvant Therapy (Radiation and/or Hormone Therapy) [within 18 months of radical prostatectomy]

   Adjuvant will be defined as preceding biochemical recurrence (BCR) (i.e.: PSA ≥ 0.2 ng/ml) and within 18 months of radical prostatectomy.

Secondary Outcome Measures

1. Time (From Randomization) to Adjuvant Treatment Administration [Up to 18 months post randomization]

   Adjuvant treatment (radiation and/or hormone) is defined as preceding BCR. BCR occurs when prostate specific antigen (PSA) ≥ 0.2 ng/ml.

2. Time (From Randomization) to Salvage Treatment Administration [Up to 5 years post randomization]

   Salvage treatment (radiation and/or hormone therapy) is defined as either after BCR or >18 months after surgery in the absence of documented BCR

3. Time (From Randomization) to Biochemical Recurrence (BCR) [Up to 5 years post randomization]

   BCR is defined as PSA ≥ 0.2 ng/ml.

4. Time (From Randomization) to Metastatic Disease (Regional or Distant) [Up to 5 years post randomization]

   Metastasis is determined based on CT, MRI, bone scan, and/or positron emission tomography (PET) scan

5. Michigan Urological Surgery Improvement Collaborative (MUSIC) Patient Reported Outcomes (PRO) [Up to 24 months post radical prostatectomy]

   Composite Expanded Prostate Cancer Index Composite (EPIC)-26 domain scores for a) urinary irritative function, b) urinary incontinence, and c) sexual function will be measured at baseline and 24 months post-radical prostatectomy. Each of the 3 domains is scaled from 0-100 (higher is better).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Prostate cancer patients who have undergone radical prostatectomy

• PSA < 0.1 ng/ml at enrollment

• At least one of the following:

• pT3 (seminal vesicle invasion or extraprostatic extension), or

• Positive surgical margins

• Radical prostatectomy within one year of enrollment

Exclusion Criteria:

• Individuals who have any of the following will not be eligible to participate:

• Have regional or distant metastatic disease

• Received any radiation or hormone therapy (neo-adjuvant, adjuvant, or salvage)

• Node positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Hospital and Health Systems	Ann Arbor	Michigan	United States	48109
2	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	Henry Ford Hospital	Detroit	Michigan	United States	48202
4	Urologic Consultants	Grand Rapids	Michigan	United States	49503
5	Urology Associates of Grand Rapids	Grand Rapids	Michigan	United States	49503
6	Michigan Urological Clinic	Grand Rapids	Michigan	United States	49546
7	Spectrum Health Medical Group- Urology	Grand Rapids	Michigan	United States	49546
8	Urology Surgeons, PC	Grand Rapids	Michigan	United States	49546
9	Comprehensive Medical Center, PLLC	Royal Oak	Michigan	United States	48073
10	Tri-City Urology	Saginaw	Michigan	United States	48601
11	Bay Area Urology Associates, PC	Traverse City	Michigan	United States	49684
12	Michigan Institute of Urology-Town Center	Troy	Michigan	United States	48084
13	IHA Urology at St. Joe's Ann Arbor	Ypsilanti	Michigan	United States	48197

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center
• Michigan Urological Surgery Improvement Collaborative (MUSIC)
• GenomeDx Biosciences Corp

Investigators

• Principal Investigator: Todd Morgan, MD, University of Michigan
• Principal Investigator: Michael Cher, MD, Wayne State University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 23, 2020

More Information

Additional Information:

• Website for MUSIC
• Website for GenomeDx Biosciences (study sponsor)

Publications

• Adams G, Gulliford MC, Ukoumunne OC, Eldridge S, Chinn S, Campbell MJ. Patterns of intra-cluster correlation from primary care research to inform study design and analysis. J Clin Epidemiol. 2004 Aug;57(8):785-94. Review.
• Badani K, Thompson DJ, Buerki C, Davicioni E, Garrison J, Ghadessi M, Mitra AP, Wood PJ, Hornberger J. Impact of a genomic classifier of metastatic risk on postoperative treatment recommendations for prostate cancer patients: a report from the DECIDE study group. Oncotarget. 2013 Apr;4(4):600-9.
• Badani KK, Thompson DJ, Brown G, Holmes D, Kella N, Albala D, Singh A, Buerki C, Davicioni E, Hornberger J. Effect of a genomic classifier test on clinical practice decisions for patients with high-risk prostate cancer after surgery. BJU Int. 2015 Mar;115(3):419-29. doi: 10.1111/bju.12789. Epub 2014 Aug 11.
• Buja, A., Hastie, T. J. and Tibshirani, R. J. (1989). Linear smoothers and additive models (with discussion). Annals of Statistics, 17, 453-555.
• Campbell, Michael J., and Stephen J. Walters. How to Design, Analyse and Report Cluster Randomised Trials in Medicine and Health Related Research. John Wiley & Sons, 2014.
• Cooperberg MR, Davicioni E, Crisan A, Jenkins RB, Ghadessi M, Karnes RJ. Combined value of validated clinical and genomic risk stratification tools for predicting prostate cancer mortality in a high-risk prostatectomy cohort. Eur Urol. 2015 Feb;67(2):326-33. doi: 10.1016/j.eururo.2014.05.039. Epub 2014 Jul 2.
• Den RB, Feng FY, Showalter TN, Mishra MV, Trabulsi EJ, Lallas CD, Gomella LG, Kelly WK, Birbe RC, McCue PA, Ghadessi M, Yousefi K, Davicioni E, Knudsen KE, Dicker AP. Genomic prostate cancer classifier predicts biochemical failure and metastases in patients after postoperative radiation therapy. Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1038-1046. doi: 10.1016/j.ijrobp.2014.04.052. Epub 2014 Jul 8.
• Den RB, Yousefi K, Trabulsi EJ, Abdollah F, Choeurng V, Feng FY, Dicker AP, Lallas CD, Gomella LG, Davicioni E, Karnes RJ. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol. 2015 Mar 10;33(8):944-51. doi: 10.1200/JCO.2014.59.0026. Epub 2015 Feb 9. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416.
• Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, Bergstralh EJ, Kollmeyer T, Fink S, Haddad Z, Zimmermann B, Sierocinski T, Ballman KV, Triche TJ, Black PC, Karnes RJ, Klee G, Davicioni E, Jenkins RB. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013 Jun 24;8(6):e66855. doi: 10.1371/journal.pone.0066855. Print 2013.
• Heo M, Leon AC. Comparison of statistical methods for analysis of clustered binary observations. Stat Med. 2005 Mar 30;24(6):911-23.
• Karnes RJ, Bergstralh EJ, Davicioni E, Ghadessi M, Buerki C, Mitra AP, Crisan A, Erho N, Vergara IA, Lam LL, Carlson R, Thompson DJ, Haddad Z, Zimmermann B, Sierocinski T, Triche TJ, Kollmeyer T, Ballman KV, Black PC, Klee GG, Jenkins RB. Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol. 2013 Dec;190(6):2047-53. doi: 10.1016/j.juro.2013.06.017. Epub 2013 Jun 11.
• Klein EA, Yousefi K, Haddad Z, Choeurng V, Buerki C, Stephenson AJ, Li J, Kattan MW, Magi-Galluzzi C, Davicioni E. A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. Eur Urol. 2015 Apr;67(4):778-86. doi: 10.1016/j.eururo.2014.10.036. Epub 2014 Nov 12.
• Lake S, Kammann E, Klar N, Betensky R. Sample size re-estimation in cluster randomization trials. Stat Med. 2002 May 30;21(10):1337-50.
• Lobo JM, Dicker AP, Buerki C, Daviconi E, Karnes RJ, Jenkins RB, Patel N, Den RB, Showalter TN. Evaluating the clinical impact of a genomic classifier in prostate cancer using individualized decision analysis. PLoS One. 2015 Apr 2;10(3):e0116866. doi: 10.1371/journal.pone.0116866. eCollection 2015.
• Michalopoulos SN, Kella N, Payne R, Yohannes P, Singh A, Hettinger C, Yousefi K, Hornberger J; PRO-ACT Study Group. Influence of a genomic classifier on post-operative treatment decisions in high-risk prostate cancer patients: results from the PRO-ACT study. Curr Med Res Opin. 2014 Aug;30(8):1547-56. doi: 10.1185/03007995.2014.919908. Epub 2014 May 15.
• Nguyen PL, Shin H, Yousefi K, Thompson DJ, Hornberger J, Hyatt AS, Badani KK, Morgan TM, Feng FY. Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists. Urology. 2015 Jul;86(1):35-40. doi: 10.1016/j.urology.2015.04.004.
• Ross AE, Johnson MH, Yousefi K, Davicioni E, Netto GJ, Marchionni L, Fedor HL, Glavaris S, Choeurng V, Buerki C, Erho N, Lam LL, Humphreys EB, Faraj S, Bezerra SM, Han M, Partin AW, Trock BJ, Schaeffer EM. Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men. Eur Urol. 2016 Jan;69(1):157-65. doi: 10.1016/j.eururo.2015.05.042. Epub 2015 Jun 6.
• Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, Messing E, Forman J, Chin J, Swanson G, Canby-Hagino E, Crawford ED. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol. 2009 Mar;181(3):956-62. doi: 10.1016/j.juro.2008.11.032. Epub 2009 Jan 23.
• Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making. 2006 Nov-Dec;26(6):565-74.
• Wu S, Crespi CM, Wong WK. Comparison of methods for estimating the intraclass correlation coefficient for binary responses in cancer prevention cluster randomized trials. Contemp Clin Trials. 2012 Sep;33(5):869-80. doi: 10.1016/j.cct.2012.05.004. Epub 2012 May 22.
• Yamoah K, Johnson MH, Choeurng V, Faisal FA, Yousefi K, Haddad Z, Ross AE, Alshalafa M, Den R, Lal P, Feldman M, Dicker AP, Klein EA, Davicioni E, Rebbeck TR, Schaeffer EM. Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer. J Clin Oncol. 2015 Sep 1;33(25):2789-96. doi: 10.1200/JCO.2014.59.8912. Epub 2015 Jul 20.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT02783950
• Other Study ID Numbers: UMCC 2016.020; CU 008; HUM00110858
• First Posted: May 26, 2016
• Last Update Posted: Nov 3, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Michigan Rogel Cancer Center: Genomics; Adjuvant Treatment
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	GC (Decipher) Arm	Usual-Care-Based (UC) Arm
Arm/Group Description	If enrolled during the Genomic Classifier (GC) period, both subjects and their treating physician will be provided GC (Decipher Prostate Cancer Classifier from GenomeDx) and CAPRA-S scores following prostatectomy.	If enrolled during the UC period, only the CAPRA-S results will be provided.
Period Title: Overall Study
STARTED	182	174
COMPLETED	175	165
NOT COMPLETED	7	9

Baseline Characteristics

Arm/Group Title	GC (Decipher) Arm	Usual-Care-Based (UC) Arm	Total
Arm/Group Description	If enrolled during the Genomic Classifier (GC) period, both subjects and their treating physician will be provided GC (Decipher Prostate Cancer Classifier from GenomeDx) and CAPRA-S scores following prostatectomy.	If enrolled during the UC period, only the CAPRA-S results will be provided.	Total of all reporting groups
Overall Participants	182	174	356
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (6.5)	64.6 (6.3)	64.7 (6.5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	182 100%	174 100%	356 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 1.1%	2 1.1%	4 1.1%
Not Hispanic or Latino	149 81.9%	147 84.5%	296 83.1%
Unknown or Not Reported	31 17%	25 14.4%	56 15.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.6%	1 0.3%
Asian	1 0.5%	2 1.1%	3 0.8%
Native Hawaiian or Other Pacific Islander	4 2.2%	0 0%	4 1.1%
Black or African American	15 8.2%	11 6.3%	26 7.3%
White	140 76.9%	140 80.5%	280 78.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	22 12.1%	20 11.5%	42 11.8%
Prostate Specific Antigen (ng/ML) [Median (Full Range) ]
Median (Full Range) [ng/ML]	6.6	6.0	6.4

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Receive Adjuvant Therapy (Radiation and/or Hormone Therapy)
Description	Adjuvant will be defined as preceding biochemical recurrence (BCR) (i.e.: PSA ≥ 0.2 ng/ml) and within 18 months of radical prostatectomy.
Time Frame	within 18 months of radical prostatectomy

Outcome Measure Data

Analysis Population Description

Includes all patients who were followed for at least 18 months or had an event prior to 18 months

Arm/Group Title	GC (Decipher) Arm	Usual-Care-Based (UC) Arm
Arm/Group Description	If enrolled during the Genomic Classifier (GC) period, both subjects and their treating physician will be provided GC (Decipher Prostate Cancer Classifier from GenomeDx) and CAPRA-S scores following prostatectomy.	If enrolled during the UC period, only the CAPRA-S results will be provided.
Measure Participants	175	165
Count of Participants [Participants]	19 10.4%	12 6.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GC (Decipher) Arm, Usual-Care-Based (UC) Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Time (From Randomization) to Adjuvant Treatment Administration
Description	Adjuvant treatment (radiation and/or hormone) is defined as preceding BCR. BCR occurs when prostate specific antigen (PSA) ≥ 0.2 ng/ml.
Time Frame	Up to 18 months post randomization

Outcome Measure Data

Analysis Population Description

Population includes patients who had adjuvant treatment

Arm/Group Title	GC (Decipher) Arm	Usual-Care-Based (UC) Arm
Arm/Group Description	If enrolled during the Genomic Classifier (GC) period, both subjects and their treating physician will be provided GC (Decipher Prostate Cancer Classifier from GenomeDx) and CAPRA-S scores following prostatectomy.	If enrolled during the UC period, only the CAPRA-S results will be provided.
Measure Participants	19	12
Median (Full Range) [days]	259	233.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GC (Decipher) Arm, Usual-Care-Based (UC) Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Wilcoxon Rank Test p-value
	Comments

3. Secondary Outcome

Title	Time (From Randomization) to Salvage Treatment Administration
Description	Salvage treatment (radiation and/or hormone therapy) is defined as either after BCR or >18 months after surgery in the absence of documented BCR
Time Frame	Up to 5 years post randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time (From Randomization) to Biochemical Recurrence (BCR)
Description	BCR is defined as PSA ≥ 0.2 ng/ml.
Time Frame	Up to 5 years post randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Time (From Randomization) to Metastatic Disease (Regional or Distant)
Description	Metastasis is determined based on CT, MRI, bone scan, and/or positron emission tomography (PET) scan
Time Frame	Up to 5 years post randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Michigan Urological Surgery Improvement Collaborative (MUSIC) Patient Reported Outcomes (PRO)
Description	Composite Expanded Prostate Cancer Index Composite (EPIC)-26 domain scores for a) urinary irritative function, b) urinary incontinence, and c) sexual function will be measured at baseline and 24 months post-radical prostatectomy. Each of the 3 domains is scaled from 0-100 (higher is better).
Time Frame	Up to 24 months post radical prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	18 months
Arm/Group Title	GC (Decipher) Arm		Usual-Care-Based (UC) Arm
Arm/Group Description	If enrolled during the Genomic Classifier (GC) period, both subjects and their treating physician will be provided GC (Decipher Prostate Cancer Classifier from GenomeDx) and CAPRA-S scores following prostatectomy.		If enrolled during the UC period, only the CAPRA-S results will be provided.
All Cause Mortality
	GC (Decipher) Arm		Usual-Care-Based (UC) Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/182 (1.1%)		0/174 (0%)
Serious Adverse Events
	GC (Decipher) Arm		Usual-Care-Based (UC) Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/182 (0%)		0/174 (0%)
Other (Not Including Serious) Adverse Events
	GC (Decipher) Arm		Usual-Care-Based (UC) Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/182 (0%)		0/174 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.