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Collection and Measurement of Biomarkers in Prostate Cancer Radiotherapy Patients (COMBINE)

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ClinicalTrials.gov Identifier: NCT02997709
Recruitment Status : Recruiting
First Posted : December 20, 2016
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Alan Pollack, University of Miami

Tracking Information
First Submitted Date  ICMJE December 15, 2016
First Posted Date  ICMJE December 20, 2016
Last Update Posted Date June 19, 2019
Actual Study Start Date  ICMJE June 24, 2016
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
Comparison of Pre- and Post-Treatment Quantitative Imaging Parameters to Changes in Circulating Tumor Cells Over Time in Study Participants. [ Time Frame: Baseline, within 8 Days Prior to End of RT, 3 months Post-RT, 9 months and 2-2.5 Years Post-RT ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
Comparison of Pre- and Post-Treatment Quantitative Imaging Parameters to Changes in Circulating Tumor Cells Over Time in Prostate Cancer Patients Receiving Radiation Therapy (RT) with or without Androgen Deprivation Therapy per standard of care. [ Time Frame: Baseline, 8 Days Prior to End of RT, 3 months Post-RT, 9 months and 2-2.5 Years Post-RT ]
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) 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.
Change History Complete list of historical versions of study NCT02997709 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • Relationship of CTC changes and/or quantitative imaging parameter changes to patient outcome (biochemical and clinical disease failure). [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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.
  • Relationship of Androgen Deprivation Therapy (ADT) status to quantitative imaging features and/or CTC levels in patients [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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.
  • 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. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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.
  • Comparison of changes in CTCs to endpoint prostate research biopsy status. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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).
  • Comparison of changes in quantitative imaging characteristics to endpoint prostate research biopsy status. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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).
  • Comparison of changes in gene expression patterns to endpoint prostate research biopsy status. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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).
  • Determination of the added value of PET/CT using newer tracers to MRI [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
  • Relationship of CTC changes and/or quantitative imaging parameter changes to patient outcome (biochemical and clinical disease failure). [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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.
  • Relationship of Androgen Deprivation Therapy (ADT) status to quantitative imaging features and/or CTC levels in patients receiving radiation therapy. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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.
  • Relationship of quantitative imaging characteristics and/or CTC changes with other tissue biomarkers (e.g., gene expression signatures) obtained from the pre-treatment MRI ultrasound (US) fusion guided prostate. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    • Gene expression data obtained at baseline will be analyzed in order to investigate the relationship between the gene expression and the following: CTCs, imaging parameters of mpMRI, 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.
  • Comparison of changes in CTC, quantitative imaging characteristics and gene expression patterns to endpoint prostate research biopsy status. [ Time Frame: Between Baseline and 2-2.5 Years Post-RT ]
    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, circulating tumor cell (CTC) changes, and/or pretreatment biopsy tissue gene expression patterns with the endpoint prostate research biopsy status.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Collection and Measurement of Biomarkers in Prostate Cancer Radiotherapy Patients
Official Title  ICMJE Collection and Measurement of Blood and Imaging Biomarkers in Patients Undergoing Standard Primary and Postoperative Radiotherapy for Prostatic Neoplasms - The Miami CoMBINe Trial
Brief Summary Prostate cancer is the most common malignancy in men and nearly 30,000 men die from the disease each year. Not only is there significant mortality, there is considerable morbidity from primary and salvage therapies. Understanding which patients require intensified treatment, as well as those who may not, would improve outcomes on multiple levels. The cohort to be investigated will be composed of men diagnosed with prostate cancer who are planned to be treated with (i) external beam radiotherapy to the prostate (primary treatment) (ii) prostatectomy (added in amendment) or (iii) postoperative radiotherapy (adjuvant or salvage treatment post-prostatectomy). Adjuvant postoperative radiotherapy is defined as men having a PSA<0.1 ng/mL and salvage postoperative radiotherapy as those having a PSA ≥0.1. The overarching objective of the CoMBINe trial is to identify pre-treatment and post-treatment prognostic and predictive factors derived from quantitative imaging prostate or prostate bed features, tumor tissue gene expression signatures, and circulating tumor cells (CTCs). The CoMBINe trial is a sister trial to another study, termed BLaStM (IRB# 20140627), in men who are candidates for primary radiotherapy. CoMBINe also allows for men with oligometastasis from prostate cancer who are treated to all sites of known disease by radiotherapy and/or surgery.
Detailed Description

Treatment: Prostatectomy, radiotherapy technique, radiotherapy dose, and the use of androgen deprivation therapy (ADT), are per the standard of care at the University of Miami, and are not specified in this protocol.

Measurements: Prior to treatment and at 3 months, 6 months, and at 2.0-2.5 years after treatment, the patients will have blood drawn for CTCs and additional blood stored for future studies. Multiparametric MRI (mpMRI) and potentially PET/CT (depending on funding) will be done at these same time points. Health related quality of life is also being assessed at these time points.

Overarching goal: To determine the relationships to quantitative imaging features (imaging biomarkers) to blood based biomarkers and tissue based gene expression marker/signatures, as well as to patient outcome.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Procedure: Blood Specimen Collection
    Blood specimen collection (plasma and serum) for CTCs and other possible biomarkers pre-radiation therapy at Baseline, during treatment and at various intervals post-treatment, per study protocol.
  • Behavioral: Memorial Anxiety Scale for Prostate Cancer patients
    Memorial Anxiety Scale for Prostate Cancer (MAX-PC) patients administered to study participants at Baseline and at intervals during treatment and post-follow-up, per study protocol.
    Other Name: MAX-PC
  • Behavioral: Expanded Prostate Cancer Index Composite-SF-12
    Expanded Prostate Cancer Index Composite (EPIC) Short Form 12 (SF-12) administered to study participants at Baseline and at intervals during treatment and post-follow-up, per study protocol.
    Other Name: EPIC-SF-12
  • Behavioral: International Prostate Symptom Score
    International Prostate Symptom Score (IPSS) administered to study participants at Baseline and at intervals during treatment and post-follow-up, per study protocol.
    Other Name: IPSS
  • Device: MRI-US fusion guided biopsy
    MRI-US fusion guided biopsy (MUFgBx) of prostate for research at baseline and 2-2.5 years post-treatment.
    Other Name: MUFgBx
  • Device: Multiparametric MRI
    Multiparametric MRI at Baseline and various time points post-treatment per study protocol.
    Other Name: mpMRI
Study Arms  ICMJE Experimental: COMBINE Patients
  • Blood specimen collection
  • Expanded Prostate Cancer Index Composite-SF-12
  • Memorial Anxiety Scale for Prostate Cancer patients
  • International Prostate Symptom Score
  • Multiparametric MRI (mpMRI) of the prostate
  • MRI-US fusion guided biopsy
Interventions:
  • Procedure: Blood Specimen Collection
  • Behavioral: Memorial Anxiety Scale for Prostate Cancer patients
  • Behavioral: Expanded Prostate Cancer Index Composite-SF-12
  • Behavioral: International Prostate Symptom Score
  • Device: MRI-US fusion guided biopsy
  • Device: Multiparametric MRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 5, 2018)
144
Original Estimated Enrollment  ICMJE
 (submitted: December 15, 2016)
300
Estimated Study Completion Date  ICMJE June 2026
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Pathologic confirmation of prostate cancer.
  2. Any T-stage.
  3. By imaging or clinical criteria, any patient with disease staging of N0/N1 and M0/M1.

    • Patients with metastatic disease are encouraged to participate.
  4. Any Gleason Score will be eligible.
  5. 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).
  6. 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.
  7. No previous pelvic radiotherapy.
  8. The ability to understand and the willingness to sign a written informed consent document
  9. Zubrod performance status ≤ 2 (Karnofsky or ECOG performance status may be used to estimate Zubrod):
  10. Age ≥ 30 at signing of consent.
  11. Subjects must be planned to receive radiation therapy or to undergo prostatectomy.
  12. Subjects treated primarily with RT are recommended to have had an MUFgBx prior to radiation treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02997709
Other Study ID Numbers  ICMJE 20150452
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: We have not developed a plan yet for IPD data sharing; although, our protocol and consent indicate plans to do so in the future after publication.
Responsible Party Alan Pollack, University of Miami
Study Sponsor  ICMJE University of Miami
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alan Pollack, MD, Ph.D. University of Miami
PRS Account University of Miami
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP