A Prospective Comparative Study of Outcomes with Proton and Photon Radiation in Prostate Cancer (COMPPARE) - Third Annual COMPPARE Workshop: ...

A Prospective Comparative Study of
Outcomes with Proton and Photon Radiation
in Prostate Cancer (COMPPARE)
Third Annual COMPPARE Workshop:
Recruitment, Retention, Maximizing Value
Amelia Island
March 22-24, 2019
Nancy Price Mendenhall, PI

COMPPARE Third Annual Workshop
• Workshop mechanics
• COMPPARE Coordinating Team
• Agenda
• Update
• Theme and Goals

Third Annual COMPPARE Workshop

COMPPARE Workshop Mechanics
    • Packets
         • Background information plus sample contributions from Keynote speakers
         • Instructions on how to claim CME/CEU

    • Attendees
         • COMPPARE Patient Stakeholders and Caregivers, Physician Co-Investigators, representatives from our
           Executive Board and Minority Engagement Committees, Physicists and our ATC partners, Clinical research
           coordinators, Vendor Stakeholders, Insurance Stakeholders, Coordinating Center Staff
         • PCORI, VA, NCCN, ACS

    • Agenda Tracks
    • Keynotes
         • National figures with unique knowledge and perspective to provide context for COMPPARE

Third Annual COMPPARE Workshop

COMPPARE Coordinating Center Team

    • http://comppare.org
    • On-site team available to assist you, all in black
      COMPPARE shirts

Update on COMPPARE Progress

Third Annual COMPPARE Workshop

COMPPARE
COMPPARE
    • This is the third annual COMPPARE workshop:
         o The first dealt with assembling the team to apply to PCORI for funding
         o The second dealt with developing the protocol and processes
         o This third deals is meant to prepare sites for study activation

    • A Prospective COMparative Study of Outcomes with Proton and Photon Radiation in
      Prostate Cancer (COMPPARE)
    • Design: large pragmatic comparative trial using parallel non-randomized cohorts with a
      randomized fractionation study embedded in the proton cohort
    • Hypothesis: small differences in patient-reported quality of life outcomes, physician
      reported toxicity interventions, and disease control between proton and photon cohorts

COMPPARE: Outcome Comparison in Parallel
Patient Cohorts
Design based on                             Patients     • Patients enter
patient engagement
                             Patients
                                          planned for      study after choice
to maximize rapid          planned for                     of Protons or
accrual by avoiding           IMRT         PROTONS         Photons
issues of:                                               • Non-randomized
• MD equipoise                                             parallel cohorts
• Institution                                            • Pragmatic SOC
   disincentives                                           (Standard Of Care)
• Patient choice           COMPPARE       COMPPARE         treatment
• Insurance denial         Enrollment     Enrollment     • Comparison of
Participating                                              Outcomes:
   institutions selected                                     •   Patient reported
                                                                 quality of life
   based on similarity
                                                             •   Physician reported
   in demographics to                                            toxicity
   minimize necessary                                            interventions
   propensity              IMRT cohort   Proton Cohort       •   Disease control:
                                                                 freedom from PSA
   adjustment                                                    progression

COMPPARE Development Workshop

2/2-4/2018: Second Annual COMPPARE Workshop: develop consensus on key elements of COMPPARE protocol

Milestones
• 4/1/2018: Contract executed between PCORI and UF which includes Milestones
• Milestones required by PCORI for monitoring site activation, accrual, data deliverables
• Important in era where many trials fail to meet accrual projections
• All other ongoing NCI (6) and PCORI (1) comparative proton vs photon trials are
  structure as randomized trials and all are behind in accrual, a point made by the NCI
  director at our national radiation oncology meeting in October 2018
• COMPPARE is designed to be patient centric and avoid most accrual barriers
  (randomization, insurance) by having patient enter after treatment is selected
• Rapid accrual is desirable to capture a broad brush stroke of practice outcomes
  (before there are changes in practice patterns)

COMPPARE History
4/1-7/1/2018: Protocol review (iterative process) and approval by
following committees at PI site, University of Florida (UF)
           Cancer Center Disease Site Group
           Scientific Review and Monitoring Committee
           Research Administration and Compliance
           UF Privacy Office
           Radiation Safety Committee
           Institutional Review Board

Milestones
7/1/18: University of Florida (UF) IRB Approval & Activation √
7/5/18-7/10/18: First patient consented and enrolled at UFHPTI √
7/5/18-3/18/2019 (9 months, 75% year):
255 prostate cancer patients screened at UFHPTI
      113 consented1 (18 screen failures, 80 currently enrolled and
15 in pre-enrollment phase2)
          142 were not consented3
1 Including 104 white, 8 black, and 1 Asian
2 While 113 is exactly on target (75% of the our projected annual accrual of 150), 95 (actual enrolled & pre-

enrolled) is ~84% of projected.
3 Including 4 Asian, 36 black, 101 white, and one who refused racial identification

1 Ineligible

Milestones
                                                     (74)
                                               28-very high risk or mets
                                               1---very low risk
                                               14-age/life expectancy6 m ADT
                                         2 Not offered (56)
      Ineligible1-74                           13-Insurance did not cover (VA-6, com-7)
      Not Offered2-56                          12-Concerns about compliance
                                               12-Active surveillance-3 or treatment elsewhere-9
      Refused3-12                              International patient
                                               6-Nursing time/missed
Opportunities to increase enrollment           4-competing research study
                                               7-Hip replacement
      clarification of ineligibility ✓         2-history of sarcoma/colon ca
                                         3 Refused (12) (12/12+113 =

      increased nursing/crc training ✓         1-family/cultural
                                               5-decline participation in any research
      new video for informed consent ✓         4-logistics burden
                                               2-too much burden with PARTIQoL

Milestones
Embedded Randomized Fractionation study within Proton Cohort
     Overall study requires 900 patients (60% of the 1500 Proton
Cohort)
         7/5/18-3/18/2019 (9 months, 75% year): UFHPTI experience
         56/113 (50%) consented
         34/80 (43%) are enrolled

1 We are slightly below our needed 60% RCT acceptance rate, although rate of acceptance is increasing
2 We believe there are opportunities to improve this rate through the newly available video and physician

training in the informed consent process, which will be addressed in the 3rd Physician breakout session

Milestones
4/1/19: All sites (should be) activated….
3/1/20: All patients (should be) accrued…….
3/3/23: All patients (should ) have 3 years of follow-up information
4/1/23: End of PCORI contract (and funding)
10/1/23: Final report due to PCORI

Milestones
4/1/19: All sites (should be) activated…. X
• UF required non-disclosure agreement1 with all sites (not budgeted) resulting in a 3-6 month delay in
  getting contracts/protocol to sites for execution and IRB approval: All NDAs were completed by
  1/7/2018
• Second of the remaining 40 sites activated on 1/18/19
• First non-UFHPTI patient consented on 2/25 and enrolled 3/7/2019
• Ten contracts2 have been executed and all remaining sites are in contracting or IRB approval process
• Six sites are very close to activation.
• PCORI understands the NDA delay, but we need to get back on track with Milestones as quickly as the
  IRB and Contracting process at each site permits
• 3/1/20: All patients (should be) accrued…….not impossible but very challenging………..

1 Many sites were confused by the NDA as it was a new requirement
2 Some sites required a Publication Policy (now created) before signing contract

Third Annual COMPPARE Workshop

Themes: Recruitment, Retention, Value
• Recruitment
    o Large number of patients because hypothesized differences are relatively small-3000 men,
      1500 per arm
    o Rapid accrual needed: to minimize impact of practice changes in SOC (standard of care)
    o Eligibility: designed to maximize chance patient can contribute ≥10 years of data

• Retention
    o Although primary study endpoint occurs at 2 y, value of data increases with length of
      observation as late effects occur, so retention is critical

• Maximizing the Value of COMPPARE
    o These large cohorts in whom treatment and outcomes will be known can contribute to our
      understanding of many other important things about prostate cancer

Third Annual COMPPARE Workshop

Goals: Making COMPPARE Work
• Patient Stakeholders
    o Understand underlying ethics and regulatory protection for human subject research
    o Understand how best to advocate for COMPPARE and aid in recruitment and retention
    o Provide patient perspective to COMPPARE team on informed consent process and
      companion studies to maximize the value of COMPPARE

• Clinical Research Coordinators
    o Increase understanding of data requirements and collection process

• Physician/Physics Teams
    o Know best SOC clinical practices
    o Know how to help CRC’s gather most accurate and complete data

Third Annual COMPPARE Workshop

CME/CEU Learning Objectives
As a result of this activity, participants will be able to
    • Describe the underlying ethical and regulatory requirements governing
      human subject research and understand best practices in advocacy for the
      COMPPARE trial
    • Describe the eligibility requirements for participating in COMPAPRE and
      attain proficiency in the use of VISIONTREE (VTOC), the web-based data
      accrual system
    • Describe the value of the COMPPARE trial for filling the evidence gap in
      knowledge about best radiation treatment for prostate cancer and describe
      current best radiation practices