160 likes | 173 Views
This paper proposes a framework for device-based, minimally invasive cancer therapies using real-time intra-procedural imaging. It explores the potential clinical utilities in interventional oncology and highlights the need for clinical trials support in this field.
E N D
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
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.
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
Molecular Imaging (and Intervention?) Imaging Probe Cell Targeted Therapy Molecular Signature of Cancer Imaging Device (IGI Device?)
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)
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
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
Clinical Trials Nomenclature:Phase 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
Clinical Trials Construct:A 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
IO Clinical Trial Endpoints:Definitions of Success and Failure • IO Therapies often repeatable • Consider adoption of vascular definitions: • Primary Success – result post intent to treat • Primary Assisted Success – add’l 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
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.
NCI IO Initiatives:IO 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
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
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
Phase II / III Infrastructure:Current “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
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