NCI Phase III Treatment Portfolio in Prostate Cancer: Opportunities for Embedding Surrogate Endpoint

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NCI Phase III Treatment Portfolio in Prostate
Cancer Opportunities for Embedding Surrogate
Endpoint Questions

• Alison Martin, M.D.
• Cancer Therapy Evaluation Program
• National Cancer Institute

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Potential Strengths of Clinical Trials Database

• Randomized trials with well defined cohorts, high
  quality follow-up, defined treatment
• RTOG 92-02
• S9916 and TAX 327 survival benefit from
  docetaxel
• Significant longitudinal databases
• Allowed progress in hypothesis generation

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Limitations of Clinical Trials Database

• Population Issues
• Disease-states
• Stage migration
• Design Issues
• Not prospectively designed to ask a surrogate
  question
• Schedule for collection of PSA (or bone) data not
  sufficiently specific
• Methodology issues migration, lack of
  standardization and reporting
• Treatment Issues
• Interaction with potential surrogate
• Lack of effective treatments to allow validation
  of a surrogate
• Challenges to Coordinating Datamining across
  Trials

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Trial Design Issues Defining the Role of PSA

• As eligibility criterion, i.e., prognostic factor
• As outcome measure which outcome?
• Cure
• Clinical Metastases
• Symptomatic metastases
• Survival
• Prostate Cancer Specific Mortality
• Which PSA parameter to use?
• Nadir, proportional decline, change in
  slope/kinetic parameter, response duration
• Magnitude of change, strength of association

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Opportunities for Embedding Surrogate Questions

• 6-7 approved treatment concepts for phase III
  treatment trials
• Projected to open 2005, facilitated by
• Collaborative NCI-FDA concept review
• Electronic protocol development with iterative
  review
• Trials in each clinical state

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Phase III Concepts by Clinical State
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Strategies to Maximize the Return from Clinical
Trials of Therapeutics

• Nest surrogate question(s) in therapeutic trials
• Informed by analyses of prior databases
• Prioritize most robust hypotheses harmonize in
  relevant trials
• Assess surrogacy for survival and other important
  outcomes
• Power considerations
• Create comprehensive database/platform for
  subsequent interrogation across trials and
  therapeutics
• Harmonize collection of essential data
• Facilitate hypothesis generation
• Specimen Banking for new biomolecular markers
• Expand Partnerships
• Prospective collaboration with industry re.
  surrogate questions and data collection
• NCI Cancer Diagnosis Program (Program for
  Assessment of Clinical Cancer Trials, PACCT)