Collection and Measurement of Biomarkers in Prostate Cancer Radiotherapy Patients

Study Overview
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Brief Summary
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The purpose of this research study is to learn about: 1) How standard radiation treatment to prostate (primary radiotherapy) or the pelvis after prostatectomy (postoperative radiotherapy) may cause changes in MRI and PET imaging traits that might be used in the future to predict response. 2) Comparison of such MRI and PET imaging traits with the number of circulating tumor cells (CTCs) present in the blood prior to treatment and the changes in these counts after treatment. 3) How MRI and PET imaging characteristics and changes are related to the expression of genes in the cancer tissue obtained before treatment from prostate biopsy or a prior prostatectomy before treatment. 4) How the response of prostate cancer treatment relates to the imaging and CTC changes.

Official Title
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Collection and Measurement of Blood and Imaging Biomarkers in Patients Undergoing Standard Primary and Postoperative Radiotherapy for Prostatic Neoplasms - The Miami CoMBINe Trial

Conditions
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Prostate Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic confirmation of prostate cancer. Any T-stage. By imaging or clinical criteria, any patient with disease staging of N0/N1 and M0/M1. Patients with metastatic disease are encouraged to participate. Any Gleason Score will be eligible. Androgen deprivation therapy (ADT) is at the discretion of the treating physician, but must be declared as none, short-term, long-term, or extended prior to enrollment. The length is calculated from the LHRH (agonist injection). If ADT is planned (based on treating physician preference), the following restrictions apply: Short term ADT is defined as ≤ 7 months; Long term ADT is defined as > 7 months and ≤ 36 months; Extended ADT is defined as >36 months (e.g., M1 patients). Prostate-specific antigen (PSA) ≤100 ng/mL within (+/-) 4 months of signing of consent. If PSA was above 100 and drops to <100 with antibiotics, this is acceptable for enrollment. No previous pelvic radiotherapy. The ability to understand and the willingness to sign a written informed consent document Zubrod performance status ≤ 2 (Karnofsky or ECOG performance status may be used to estimate Zubrod): Age ≥ 30 at signing of consent. Subjects must be planned to receive radiation therapy or to undergo prostatectomy. Subjects treated primarily with RT are recommended to have had an MUFgBx prior to radiation treatment.

Ages Eligible for Study
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Minimum Age: 30 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 |
| --- | --- |
| Radiation Therapy Group<br>Participants with prostate cancer diagnosis who are scheduled to undergo standard of care radiotherapy with or without the addition of Androgen Deprivation Therapy (ADT) will be evaluated | |
| Prostatectomy Group<br>Participants with prostate cancer diagnosis who are scheduled to undergo prostatectomy will be evaluated | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Pre- and Post-Treatment Quantitative Imaging Parameters to Changes in Circulating Tumor Cells Over Time in Study Participants. | Pre-Treatment and Post-Treatment quantitative imaging parameters will be associated with circulating tumor cell (CTC) changes over time in prostate cancer (PCa) patients who receive treatment with RT ± androgen deprivation therapy (ADT) or prostatectomy per standard of care. CTC and quantitative imaging changes will be determined at each of the planned research acquisition time points (8 days prior to completion of radiation therapy (RT), 3 months post-RT, 9 months post-RT, and 2-2.5 years post-treatment) comparing to the Baseline. | Baseline, within 8 Days Prior to End of RT, 3 months Post-RT, 9 months and 2-2.5 Years Post-RT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship of CTC changes and/or quantitative imaging parameter changes to patient outcome (biochemical and clinical disease failure). | CTC changes between baseline and 2-2.5 years will be compared with 2-2.5 year biopsy positivity status (positive vs. negative) for patients whose baseline and 2-2.5 year biopsy samples are available. CTC changes from two different time points will be tested for significance using t-test by 2-2.5 year biopsy positivity status. Correlation structures between CTC and imaging parameters will be analyzed using linear mixed-effect model by 2-2.5 year biopsy positivity status. | Between Baseline and 2-2.5 Years Post-RT | 
| Relationship of Androgen Deprivation Therapy (ADT) status to quantitative imaging features and/or CTC levels in patients | Change of CTC and imaging parameters at a specific time point from baseline will be compared by ADT status (yes vs. no) using t-test. Correlation structure between CTC and imaging parameters will be analyzed using linear mixed-effect model by ADT status. | Between Baseline and 2-2.5 Years Post-RT | 
| Relationship of quantitative imaging characteristics and/or CTC changes with other tissue biomarkers obtained from the pre-treatment MRI ultrasound (US) fusion guided prostate biopsy or prostatectomy tissue in those treated primarily. | Gene expression data obtained at baseline will be analyzed in order to investigate the relationship between the gene expression and the following: CTCs, mpMRI imaging parameters, histopathological tumor parameters, and biochemical/clinical failure. CTC changes between baseline and 2-2.5 years will be compared with 2-2.5 year biopsy positivity status (positive vs. negative) for patients whose baseline and 2-2.5 year biopsy samples are available. CTC changes from two different time points will be tested for significance using t-test by 2-2.5 year biopsy positivity status. Changes in gene expression and imaging parameters will be analyzed in the same manner. Correlation structures between CTC and imaging parameters; CTC and gene expression; and imaging parameters and gene expression will be analyzed using linear mixed-effect model by 2-2.5 year biopsy positivity status. | Between Baseline and 2-2.5 Years Post-RT | 
| Comparison of changes in CTCs to endpoint prostate research biopsy status. | In patients who have undergone the MRI-US fusion guided biopsy (MUFgBx) at 2-2.5 years after all planned treatment, to investigate the relationship of circulating tumor cell (CTC) changes with the endpoint of research prostate biopsy status (only for those who are treated primarily with RT, who are not on indefinite ADT and who agree to this prostate early endpoint biopsy). | Between Baseline and 2-2.5 Years Post-RT | 
| Comparison of changes in quantitative imaging characteristics to endpoint prostate research biopsy status. | In patients who have undergone the MRI-US fusion guided biopsy (MUFgBx) at 2-2.5 years after all planned treatment, to investigate the relationship of quantitative imaging characteristics with the endpoint of research prostate biopsy status (only for those who are treated primarily with RT, who are not on indefinite ADT and who agree to this prostate early endpoint biopsy). | Between Baseline and 2-2.5 Years Post-RT | 
| Comparison of changes in gene expression patterns to endpoint prostate research biopsy status. | In patients who have undergone the MRI-US fusion guided biopsy (MUFgBx) at 2-2.5 years after all planned treatment, to investigate the relationship of pretreatment biopsy tissue gene expression patterns with the research endpoint of prostate biopsy status (only for those who are treated primarily with RT, who are not on indefinite ADT and who agree to this prostate early endpoint biopsy). | Between Baseline and 2-2.5 Years Post-RT | 
| Determination of the added value of PET/CT using newer tracers to MRI | PET/CT using newer tracers (fluciclovine, prostate-specific membrane antigen (PSMA), or Choline) to MRI may add value in the above secondary analyses. The investigators hypothesize that targeted PET agents will enhance the rate of accuracy of mpMRI in establishing high risk areas in the prostate, prostate bed, and pelvic lymph nodes, as well as provide unique information on early metastatic disease. | Between Baseline and 2-2.5 Years Post-RT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADT, Circulating Tumor Cells, CTCs, Androgen Deprivation Therapy