Report from IUCC Associate Director for Clinical Research

1. Report from IUCC Associate Director for Clinical Research Presentation to External Advisory Committee – Sept 25, 2006

2. The Goals of the IUCC Vision • To be a leading, national comprehensive cancer center based on our scientific investigation, health care delivery, and education. Mission • IUCC seeks to reduce the burden of cancer through innovation and dissemination Goals • 1. Foster excellence in interdisciplinary translational research through established and developing research programs. • 2. Provide the highest quality patient care through interdisciplinary clinical programs. • 3. Develop nationally recognized interdisciplinary graduate and post-graduate education and training programs. • 4. Facilitate the development and implementation of a statewide cancer control program.

3. The IUCC’s Comprehensive Approach to the Cancer Continuum Diagnosis & Treatment Terminal Care Early Detection Prevention Cancer Prevention and Control Healthy Behaviors Risk Factor Behaviors Early Detection End of Life Support Survivor- ship Follow-up EDT - Breast Cancer – H,M & I Optimizing Therapeutic Efficacy Biomarker Identification Minimizing Toxicity Drug Discovery Chemoprevention

4. IUCC Organization Structure to Enhance Clinical Trial Conduct for All Disciplines

5. Clinical Research Committee • Representatives from all disciplines  Medical Oncology  Pediatrics  Behavioral  Hoosier Oncology Group  Surgery  Vice Chancellor for Research  Urology  Clinical Pharmacology • Radiation Oncology  Radiology (incl.Interventional) • Monthly Meeting (minutes provided) • SRC Chair (Croop) • CTMC and Minority Accrual (Clark, Selbe) • CRO (Lee, Bridges, Abonour, Fallon)

6. Clinical Research Committee- Chaired by AD for Clinical Research Roles/Responsibilities1)   Facilitate and oversee conduct of clinical research for all disciplines represented in the IUCC 2)   Review recommendations of the SRC and CTMC and determine policy with input based from broad membership 3) Monitor and enhance Minority Accrual 4)   To promote multidisciplinary clinical and translational investigations among laboratory, clinical, and behavioral investigators 5)   To promote consistent protocol development and uniform reporting to track accrual, adverse events, and continuing review6)   To allocate Cancer Center resources - CCSG “protocol specific research” or other Cancer Center funds to investigator initiated pilot or Phase I studies based upon scientific merit and contribution to the mission of the Cancer Center - Clinical Research Office services

7. Clinical Research and IUCC GOAL 1: Foster excellence in interdisciplinary translational research through established and developing research programs. Objective 1: Recruit key investigators (basic and clinical) to develop comprehensive disease based research groups Objective 2: Increase number and quality of investigator initiated trials with a focus on R21 Quick Trials Objective 3: Make protocol development and review process more efficient for all cancer-related disciplines

8. Foster excellence in interdisciplinary translational research • Recent key clinical recruits to enhance clinical trial accrual • Brian Schneider, MD; Breast Cancer, Clin Pharm • Gabi Chiorean, MD – GI and Phase 1 • Sherif Farag, MBBS, PhD – BMT Director • Noah Hahn, MD - GU • Daniela Matei, MD – Ovarian Cancer • John Turchi, PhD – Lung Cancer translational research

9. Fostering excellence in interdisciplinary translational research with initiatives to: 1) maximize the quality of investigator initiated trials 2) streamline protocol development process for investigators

10. Process for IUCC Support of Investigator Initiated Trials Clinical Trials as Part of Indiana University Cancer Center Translational Initiative (ITRAC)

11. Target ID - Assay Development, Phase I, II, Lead Candidate Target/Disease Screening, Lead Generation/Selection, III, Launch, Optimization Selection Validation Drugability, Assay Validation Life Cycle Clinical Trials as Part of ITRAC Clinical Product Candidate Preclinical Discovery Preclinical Discovery Launch Development Target ID Target ID - - Assay Development, Candidate Lead High Impact Clinical Trials Target/Disease Target/Disease Selection Optimization Validation Validation Target ID Drug Discovery, In Vitro Data In Vivo Data Clinical Trials Continuous PSR RFA on website, advertised in IUCC newsletter (monthly deadline, 3 pages limit, overview of concept) IUCC Investigator Initiated Concept Assessment Panel (subcommittee of CRC) Protocol specific research Non PSR IIT • Access to support for writing protocol and grant application • data-base development, CRS, RN, biostats, protocol development • Clinical core usage (imaging, PG, proteomics, genomics, PK) • Protocol Development Approved

12. Target ID - Assay Development, Phase I, II, Lead Candidate Target/Disease Screening, Lead Generation/Selection, III, Launch, Optimization Selection Validation Drugability, Assay Validation Life Cycle Clinical Trials as Part of ITRAC Clinical Product Candidate Preclinical Discovery Preclinical Discovery Launch Development Target ID Target ID - - Assay Development, Candidate Lead High Impact Clinical Trials Target/Disease Target/Disease Selection Optimization Validation Validation Target ID Drug Discovery, In Vitro Data In Vivo Data Clinical Trials • Submission of protocol to SRC • Scored (science, potential for NCI funding, phase 2) • Budget for complete protocol developed Notification to investigator of amount of support from IUCC Activation of trial • Progress report of start-up portion • Overview of science (conduct of trial, data) • Progress to extramural funding (R21 working group participation, submission)

13. PSR Requirements • A.      Nursing and CRS support to conduct and complete innovative or proof-of-principle clinical trials originating from IUCC • B.      Early phase testing of candidate drug or device to prevent, treat, diagnose or detect • C.      Short duration (less than one year) • D.      Basis for future grant support or lead to phase II or III • E.      Document oversight of budget by leadership

17. Resources Available to Facilitate Investigator Initiated Clinical Trials • Oncore • Development of electronic case report forms • Tracking accrual, SAEs, communication with IRB, SRC, ePRMS • Illumina – translational genomics facility • RNA profiling from paraffin embedded tissue (far less cumbersome than frozen samples) • Research Related Imaging • dceMRI, novel PET tracers • Clinical Pharmacology and Pharmacogenetics • HPLC-MS/MS, DNA extraction and analysis • Proteomic Facilities • MALDI/TOF, SELDI, Glycoproteomics (IU-B), Metabolomics (PU)

18. Increasing Number of R21 Quick Trials • R21 Quick Trials Working Group • NCI funding opportunity to cover cost of translational clinical trials • Implemented August 2006 • In conjunction with PSR mechanism • Core group of investigators meet to put grant together • Templates for required sections • Peer review

19. Clinical Research and IUCC GOAL 2: Provide the highest quality patient care through interdisciplinary clinical programs. Objective 1: Mapping project to maximize the clinical trial activity for the disease spectrum for all diseases Objective 2: Develop a disease and discipline based advocate program to facilitate communication across the IUCC Objective 3: Disseminate clinical trial activity and quality patient care to the community by integration of clinical programs with the Hoosier Oncology Group

20. Mapping Clinical Research at IUCC • Purpose: • Collate all clinical research in a uniform web accessible format to document research efforts along the continuum of the cancer process • Recognize the importance of all clinical research from prevention to palliation • Identify strengths and weaknesses • Identify opportunities for collaborations • Format to map out comprehensive programs from the lab to the clinic

21. IUCC Prostate Cancer Program Prevention Localized Metastatic Supportive / Correlative Local Relapse Biochemical Measurable Tx Naïve HSPC AIPC HSPC AIPC Low Risk Int. Risk High Risk E3805 ADT +/- Doc (Dr. Sweeney) No Trials No Trials RTOG 0126 70 v 79 Gy (Dr. McGarry) RTOG 0521 XRT + ADT +/- Doc (Dr. McGarry) 0102-35 HIFU (Dr. Koch) AMG 20040138 AMG162 (Dr. Sweeney) Astra-Zeneca KC + ZD6474 (Dr. Hahn) CALGB 90401 Doc +/- Bev (Dr. Sweeney) 0052 Strength Traiining (Dr. Damush) E9802 Prostvac-V/F + GMCSF (Dr. Hahn) D9902 Provenge (Dr. Gardner) 0121 Functional CT (Dr. Akisik) SWOG 9921 ADT +/- MP (Dr. Sweeney) CALGB 90202 ADT +/- Zom (Dr. Sweeney) RTOG 0518 XRT + ADT +/- Zometa (Dr. McGarry) HOG 03-67 Pemtxd 2nd line (Dr. Sweeney) 0165 PC-GRACE (Dr. Hahn) ME-CLN-006 Panzem 2nd line (Dr. Hahn) 0501-03B AA PC Screening (Dr. Sweeney) = In Development

22. Disease and Discipline Based Clinical Research Advocates • Process to Map All Research • Co-ordinate SRC submission process • Disease-based advocate GI Hematology GU Pediatrics Breast Thoracic • Discipline-based advocates • Radiation Oncology • Radiology • Behavioral • Gastroenterology

23. Mapping Clinical Research at IUCC • Roles and Responsibilities of “Advocates” • Sign off on all SRC submissions and provide annual progress report on accrual to studies and accomplishments in prior year • Ensure trials that cross disciplines trials have been reviewed by all relevant disciplines prior to submission and that a letter of support is provided by all relevant parties • eg: behavioral survivorship study in colorectal cancer will require support letter from colorectal and behavioral research advocates respectively • eg: a study requiring chemotherapy with a surgical intervention will require a surgeon and medical oncology sign-off. • Update the appropriate disease based mapping

24. Clinical Research and IUCC GOAL 2: Provide the highest quality patient care through interdisciplinary clinical programs. Objective 1: Mapping project to maximize the clinical trial activity for the disease spectrum for all diseases Objective 2: Develop a disease and discipline based advocate program to facilitate communication across the IUCC Objective 3: Disseminate clinical trial activity and quality patient care to the community by integration of clinical programs with the Hoosier Oncology Group

25. Dissemination of clinical trials into the community • Hoosier Oncology Group • 12 staff to help write and conduct clinical trials • Chairman: Christopher Sweeney, MBBS • Chief Medical Officer: Lawrence Einhorn, MD • Conduct trials in community – 30 sites accrue • Centralized IRB established • > 200 patients per year on trial • All investigator initiated; 10 open at anyone time; $2.5M per year in Investigator Initiated or Federal Support • HOG publications • Since 1983: 101 manuscripts and 44 ASCO abstracts • 1/04 - 9/06: 10 manuscripts and 13 ASCO abstracts

26. Hoosier Oncology Group • Lung Cancer • Randomized phase III trial led by Hanna and Einhorn • A Phase III Trial of Cisplatin/Etoposide/Radiotherapy With or Without Consolidation Docetaxel in Patients with Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC): Hoosier Oncology Group LUN01-24 • “The interim efficacy findings of the formal DSMB indicate that there is a very small probability that this study will ever establish a significant difference favoring either of the two arms.” • Implications for the management of NSCLC

27. Hoosier Oncology Group • Integration of Emerging Technologies • Clinical specimen collection for Sledge $10M DOD Center of Excellence grant to study proteomics and pharmacogenetics as predictor of response • Clinical specimen collection and management of NCI sponsored CPTAC grant (validate different proteomic platforms) • $7M grant in collaboration with Purdue Cancer Center

28. 180 160 140 120 100 80 60 40 20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Glycoproteins as biomarkers of response in HOG Study - Serum of Prostate Cancer Patients Baseline 24 weeks Treatment Peak Area 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Glycan Number

29. Major Accomplishments • Clinical Trial Accrual • HOG • > 200 patients per year accrued • IUCC Investigator Initiated Trials • Summary 3 – 16% (470 of 3010 patients) • Does not include compassionate use, roll-overs, reviewed to not incude correlative studies • Expanding Phase I Clinical Trial Activity • 11 “First into Human” Phase 1 trial (Jan 04 to Sept 06) • > 100 patients accrued to phase 1 trials • Leadership in ECOG • Sledge: Chairman Breast Committee • Miller: PI of two randomized phase III breast cancer trials • Sweeney: PI of randomized phase III prostate cancer trial • Hanna: PI of phase II mesothelioma trial

30. Major Accomplishments • Pediatric Trial Accrual Year Analytical Cases Accrued 2004 148 84 (57%) 2005 161 66 (41%) • Riley: Top five of all 260 COG centers • Therapeutic accrual • ~ $275,000 NCI support annually