Trial of Prostate Cancer Patients Undergoing Active Surveillance With or Without MRI-Guided Management

Study Overview
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Brief Summary
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Using multiparametric MRI Ultrasound-guided or MRI-guided biopsies will allow more accurate sampling of the tumors and therefore will increase the rate of progression on early (first and second) surveillance biopsies and decrease the rate of progression on late (third and further) surveillance biopsies compared to Transrectal Ultrasound-guided biopsies. Quality of life (QoL) will be similar in patients undergoing MRI Ultrasound or MRI-guided and Transrectal Ultrasound-guided biopsies. Biomarker expression levels will correlate with biopsy progression.

Detailed Description
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Favorable risk patients will be randomized to one of two active surveillance arms. Stratification will be based on Prostate-specific antigen density (PSAD) (=< 0.15 vs > 0.15 ng/mL per mL), and number of positive cores in the diagnostic biopsy (1 vs 2): Arm I: Active Surveillance Alone (AS). TRUS guided biopsies at start (within 6 months of enrollment) and at yearly intervals thereafter up to 36 months after the initial biopsy (maximum four biopsies). Arm II: MRI-Managed Active Surveillance (MRI-AS). MRIus or MRI-guided biopsies at start (within 6 months of enrollment) and at yearly intervals thereafter up to 36 months after the initial biopsy (maximum four biopsies). Patients will also complete Quality of Life (QoL) assessments to provide unique data on the effects of MRI monitoring for patients undergoing active surveillance on QOL. The investigators have selected a group of measures that have been used extensively in prostate cancer populations.

Official Title
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A Randomized Two-Arm Trial of Prostate Cancer Patients Undergoing Active Surveillance With or Without MRI-Guided Management: The MGM Trial

Conditions
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Prostate Cancer, Prostate Adenocarcinoma

Intervention / Treatment
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* Procedure: Transrectal Ultrasound-Guided Biopsy
* Procedure: MRI Ultrasound Biopsy
* Behavioral: Expanded Prostate Cancer index Composite Questionnaire
* Behavioral: Short-Form 12 of Health Related Quality of Life Questionnaire
* Behavioral: Memorial Anxiety Scale for Prostate Cancer
* Procedure: Plasma/Serum Sample for biomarkers
* Procedure: Urine Sample for Biomarkers
* Procedure: Blood Tests for Blood Urea Nitrogen and Creatinine
* Procedure: Blood Test for Serum PSA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy confirmed adenocarcinoma of the prostate. Biopsy must consist of at least 8 cores. Enrollment is =< 1 year from diagnosis. One or two biopsy cores with less than 50% tumor present in each core and Gleason score =< 6 (3+3). Candidate for multiparametric MRI. T1-T2a disease based on digital rectal exam. No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for >= 5 years then the patient is eligible. Ability to understand and willingness to sign a written informed consent document Zubrod performance status < 2. Patients must agree to fill out the psychosocial questionnaires. Age >= 35 and =< 75 years Exclusion Criteria: Not biopsy confirmed adenocarcinoma of the prostate. Biopsy consists of less than 8 cores. Three or more biopsy cores are positive. Gleason score >= 3+4=7. A single core has >= 50% involvement with Gleason score =6 (3+3) or less. DCE-MRI study before enrollment. Inability to undergo MRI exam. Greater than T2a disease based on digital rectal exam. Concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for < 5 years then the patient is ineligible Inability to understand or unwilling to sign a written informed consent document. Zubrod performance status >= 2. Patient unwilling to fill out the psychosocial questionnaires. Age < 35 or > 75.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AS: Active Surveillance Alone<br>Active Surveillance Alone (AS). Transrectal Ultrasound-guided biopsies within 6 months of enrollment and at 1 year intervals thereafter (maximum four biopsies). | Procedure: Transrectal Ultrasound-Guided Biopsy<br>* Active Surveillance Alone (AS). Transrectal Ultrasound-guided biopsies within 6 months of enrollment and at 1 year intervals thereafter (maximum four biopsies).<br>* Other names: TRUS;Behavioral: Expanded Prostate Cancer index Composite Questionnaire<br>* Quality of life questionnaire obtained at Baseline, and at 12, 24 and 36 months after initial biopsy<br>* Other names: EPIC;Behavioral: Short-Form 12 of Health Related Quality of Life Questionnaire<br>* Quality of life questionnaire obtained at Baseline, and at 12, 24 and 36 months after initial biopsy<br>* Other names: SF-12 HRQOL;Behavioral: Memorial Anxiety Scale for Prostate Cancer<br>* Quality of life questionnaire obtained at Baseline, and at 12, 24 and 36 months after initial biopsy<br>* Other names: MAX-PC;Procedure: Plasma/Serum Sample for biomarkers<br>* Plasma/Serum Sample for biomarkers obtained at Baseline, and at 12, 24 and 36 months after initial biopsy for correlative studies (CTC, fcDNA, SNPs)<br>Procedure: Urine Sample for Biomarkers<br>* Urine Sample for biomarkers obtained at Baseline, and at 12, 24, and 36 months for correlative studies (hypermethylated DNA)<br>Procedure: Blood Tests for Blood Urea Nitrogen and Creatinine<br>* Blood Tests for Blood Urea Nitrogen (BUN) and Creatinine obtained at 0 - 6 months, and at 12, 24, and 36 months from initial biopsy. This is optional, subject may refuse<br>Procedure: Blood Test for Serum PSA<br>* Blood test for Serum PSA obtained at Baseline, at every 6 months up to 36 months from initial biopsy.<br>* Other names: PSA test;|
| MRI-AS: MRI+ Active Surveillance<br>MRI-Managed Active Surveillance (MRI-AS). MRI Ultrasound or MRI-guided biopsies within 6 months of enrollment and at 1 year intervals thereafter (maximum four biopsies) | Procedure: MRI Ultrasound Biopsy<br>* MRI-Managed Active Surveillance (MRI-AS). MRI Ultrasound or MRI-guided biopsies within 6 months of enrollment and at 1 year intervals thereafter (maximum four biopsies)<br>Behavioral: Expanded Prostate Cancer index Composite Questionnaire<br>* Quality of life questionnaire obtained at Baseline, and at 12, 24 and 36 months after initial biopsy<br>* Other names: EPIC;Behavioral: Short-Form 12 of Health Related Quality of Life Questionnaire<br>* Quality of life questionnaire obtained at Baseline, and at 12, 24 and 36 months after initial biopsy<br>* Other names: SF-12 HRQOL;Behavioral: Memorial Anxiety Scale for Prostate Cancer<br>* Quality of life questionnaire obtained at Baseline, and at 12, 24 and 36 months after initial biopsy<br>* Other names: MAX-PC;Procedure: Plasma/Serum Sample for biomarkers<br>* Plasma/Serum Sample for biomarkers obtained at Baseline, and at 12, 24 and 36 months after initial biopsy for correlative studies (CTC, fcDNA, SNPs)<br>Procedure: Urine Sample for Biomarkers<br>* Urine Sample for biomarkers obtained at Baseline, and at 12, 24, and 36 months for correlative studies (hypermethylated DNA)<br>Procedure: Blood Tests for Blood Urea Nitrogen and Creatinine<br>* Blood Tests for Blood Urea Nitrogen (BUN) and Creatinine obtained at 0 - 6 months, and at 12, 24, and 36 months from initial biopsy. This is optional, subject may refuse<br>Procedure: Blood Test for Serum PSA<br>* Blood test for Serum PSA obtained at Baseline, at every 6 months up to 36 months from initial biopsy.<br>* Other names: PSA test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Progression in Subjects undergoing MRIus Biopsy vs Standard Ultrasound biopsy | To determine of multiparametric MRIus-guided biopsies increase the rate of progression on early (first two) biopsies in men undergoing active surveillance as compared with early detection using standard ultrasound biopsy. | 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression Levels of Biomarkers from biopsies collected with MRI-us Biopsy vs Standard Ultrasound Biopsy |  | 42 months | 
| Effect of MRI Monitoring on Health-Related Quality of Life | To determine the effect of MRI monitoring on health-related quality of life (HRQOL), prostate cancer-specific anxiety QOL (ie general, PSA-testing & recurrence anxiety, PC-Anxiety) and prostate cancer-specific QOL (ie sexual, urinary & bowel function, PC-QOL), particularly as they relate to ethnically and socioeconomically diverse and disparate populations. | 42 months |