# Presentation: 007670

## 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?)

**Molecular Signature**
**of Cancer**

**Cell**

**Targeted**
**Therapy**

**Imaging**
**Device**
**(IGI Device?)**

**Imaging**
**Probe**

## 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 OncologyImaging 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

**7****th**** 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**