A Framework for DeviceBased Clinical Research in ImageGuided Therapies

1
A Framework for Device-Based Clinical Research in
Image-Guided Therapies

• Keyvan Farahani, PhD
• Gary Dorfman, MD
• Image-Guided Interventions Branch
• Cancer Imaging Program
• NCI

2
Interventional Oncology (IO)

• IGI Defined Device-based, minimally-,
  non-invasive cancer therapies that use real-, or
  near real-time intra-procedural imaging for
  localization, targeting, monitoring, control, and
  endpoint determination.
• not just IR also RT, endoscopy, surgery, etc.

3
Interventional Oncology

• Potential Clinical Utilities
• Primary Palliation (Bone Mets, Celiac Axis Block)
• Secondary Palliation (PCN, PBD, G-, J-tubes)
• Adjunctive Therapy (PV Embolization, Access)
• Bridge to Definitive Rx (HCC)
• Cure (Early / Screen Detected CA, Pre-CA,
  Indeterminate Lesions)
• Intermediate Facilitator for Development of
  Molecularly Targeted Therapies

4
Molecular Imaging (and Intervention?)
Imaging Probe
Cell
Targeted Therapy
Molecular Signature of Cancer
Imaging Device (IGI Device?)
5
NCI Support for IO Current Environment

• CTWG / TRWG / Multi-PI Initiative
• Existing PAs
• R01 / SBIR / STTR
• Platform Development, Clinical Trials
• Now Two Quick Trials Mechanisms
• However, Current Payline is Dismal
• NCI Unique in Offering Clinical Trials Support
  Outside of Investigator Initiated Mechanisms
• I2 Imaging Initiatives, Including
• IO Clinical Trials Support
• Informatics (caBIG, NCIA, databases, analysis
  algorithms)

6
NCI IO Initiatives Current

• CIP IGI Branch Initiatives
• Largely Basic Science Through Investigator
  Initiated Pathways
• Discovery, Development, Delivery
• Translational Research (inc. Early Trials)
• Clinical Trials Infrastructure
• Targeted Towards Image-Guided, Device-Based
  Therapy Similar to the Infrastructure Provided
  for Pharmaco-therapies
• Phase 0 IV (Phase A D)
• Goal Bring Therapies with Disease-specific
  Indications to Market

7
Interventional Oncology

• Ideally Supported by Funded Research
• Discovery / development (Preclinical Phase
  0)
• Optimization (Preclinical and Phase 0 early
  II)
• Validation for specific cancers / stages (Phase
  II IV)
• Regulatory approval (Later Phase II and III)
• Supportive payor policies (Later Phase II IV)
• Widespread physician acceptance (Later Phase II
  IV)
• Patient recognition and informed demand

8
Clinical Trials NomenclaturePhase 0 IV vs.
Pilot / Pivotal

• Pharma Phase 0 IV
• Works for many but not all drug trials
• Poor fit for IGI / IO trials based on standard
  definitions procedures
• FDA/CDRH Pilot and Pivotal Designation
• Regulatory purpose
• No accepted linkage to Phase 0 IV
• Not sufficiently granular for scientific
  endpoints
• Approval process different than CDER/CBER

9
Clinical Trials ConstructA Proposed Matrix for
IO Trials

• Phase A D
• A (0 / I, Pilot) Single site safety, QA,
  effect, optimize I I lesion, organ, patient
• B (I / II, Pilot) Single / Multi-site effect,
  standardize, translate, early data lesion,
  organ, early patient level data
• C (II, Pilot / Pivotal) Multi-site
  organ/lesion outcome /or more robust patient
  level data
• D (III / IV, Pivotal) Multi-site patient level
  data, comparative, randomized preferred

10
IO Clinical Trial EndpointsDefinitions of
Success and Failure

• IO Therapies often repeatable
• Consider adoption of vascular definitions
• Primary Success result post intent to treat
• Primary Assisted Success addl Rx, different
  site
• Secondary Success re-treatment of residual /
  recurrent disease at previously treated site
• Failure residual, recurrent, new disease
• Patient Refuses or Is Ineligible for Added
  Therapy Death etc.
• Worthy of Consideration
• Local control
• Systemic control
• Intent to treat and treatment plan
• Purpose of treatment cure, long-term control,
  control as bridge therapy, palliation

11
Interventional OncologyImaging Issues RECIST,
etc.

• RECIST Criteria unless modified do not apply
• Non-IGI RECIST issues already limiting
• Immediate post-IGI lesion larger
• Imaging lesion ? disease (viable tumor)
• Recurrence / residual may not alter lesion
  dimensions
• Validation of imaging findings
• Imaging/sensing equivalent of the surgical
  tumor-free margin Future interventional
  oncology likely multi-parametric, co-registered
  data anatomic, physiologic.

12
NCI IO InitiativesIO Clinical Trials
Infrastructure

• Targeted Towards Providing an Infrastructure for
  Image-Guided, Device-Based Therapy Similar to the
  Infrastructure Provided for Pharmacotherapies
• Phase 0 IV (Phase A D)
• Goal Bring Therapies with Disease-specific
  Indications to Market
• Phase II and III Currently Implemented Through
  Existing Cooperative Groups
• Infrastructure is not All or Nothing
• Variations in Collaborative Mechanisms
• Use of NCIA to Support non-NCI Trial under
  Specific Conditions

13
NCI IO Clinical Initiatives Current

• Device Rx Strategy Meetings (2-3 / Year)
• Exploratory By Invitation Meetings (Stage I and
  II Breast Cancer)
• Open / Private Device Rx Development Meetings
  (Renal Cell Cancer)
• Disease / Technology Focused
• Multi-purpose (Multilateral Education,
  Prioritization, Potential Solicitations)
• Support for Later Phase Clinical Trials
• Collaboration among NCI, FDA, CMS
• Strong Ties with Industry (CTA, CSA, pre-IDE,
  etc.)
• Utilizes Cooperative Group Mechanism
• Two Protocols in Process NOW

14
NCI IO Clinical Initiatives Current

• 7th Annual Forum on Biomedical Imaging in
  Oncology - Feb 1-2, 2007
• Collaboration with NEMA, AdvaMed, MDMA
• Will Focus on Opportunities for Collaboration
  including Clinical Trials
• QC and Uncertainty Measurements
• SPORE and CC Initiatives
• Tissue Acquisition in Early Phase Clinical Trials
• Standardized Imaging Protocols During IO Trials
• Trans-SPORE Activities

15
Phase II / III InfrastructureCurrent
Implementation

• PI / Industry Collaborator Work Through
  Cooperative Group to Submit Concept
• Considerations - IDE, CPT, etc.
• CSA / CTA between NCI and Industry
• Concept Approved
• Pre-IDE Meeting with ODE/CDRH/FDA (include NCI,
  PI, etc.)
• Contract between Cooperative Group and Industry
• Protocol Developed
• IDE Application by NCI (if necessary)
• CMS Discussions Regarding Funding Clinical Care
• Protocol (and IDE) Approved by NCI and FDA
• Protocol Activated (Potential CTSU Listing)
• Image Support through NCIA

16
Conclusion

• IGI methods offer new challenges and
  possibilities in cancer care
• Opportunities for academia, industry, and federal
  agencies to work closely together to address
  issues and bring new therapies to the bedside