Wisconsin Oncology Network (WON)

1. Wisconsin Oncology Network (WON) Anne Traynor, MD UWCCC Heme Onc amt@medicine.wisc.edu Mary Beth Wims Lynn Volk UWCCC Central Research Office mbwims@uwcarbone.wisc.edu lmvolk@uwcarbone.wisc.edu

2. Disclosures • I, on behalf of the UW Board of Regents, receive research funding from the pharmaceutical companies listed. This support pays the salaries of the UWCCC lung cancer research staff. • Eli Lilly and Company • Novartis • Bayer Pharmaceuticals • I will discuss unapproved use of investigational agents or combinations.

3. Wisconsin Oncology Network • Collegial research network developed by the UWCCC in 1999 • Extend the conduct of investigator-initiated phase II heme/onc trials through Wisconsin • Offer innovative protocols locally • Local sites accrue roughly 1/3 to 1/2 of patients • Phase II trials estimate efficacy of a novel agent/combination in a specific disease site • Safety, tolerability, and dose previously determined in a Phase I trial • Phase II: Prostate cancer, non-Hodgkin’s lymphoma, colon cancer, etc. • Single arm phase II usually enrolls 30 – 50 pts and compares to historical controls • Newer 2 arm phase II trials randomize to investigational and control arms (about 40 - 50 per arm) in order to obtain estimates of efficacy “compared” to the concurrent control arm • Phase III trials compare novel agent to standard of care • Outreach of novel anti-cancer treatments and education is an important mission of the UW Carbone Cancer Center

4. Aurora Health Care System Bellin Cancer Team Green Bay Cancer Center at Aspirus Hosp Wausau Columbia-St. Mary’s Milwaukee Dean Clinic South Central Wisconsin Ferguson Cancer Center Freeport, IL Fox Valley Hematology/Onc Green Bay Oncology Gundersen Lutheran LaCrosse Holy Family Cancer Center Manitowoc Marshfield Clinic Medical College of Wisconsin Mercy Health Janesville Regional CC of Waukesha and Oconomowoc UWCCC: UWHC and 1 South Park in Madison UWCCC Partners Johnson Creek Wisconsin Rapids Vucurevich Cancer Center Rapid City, SD WON Members

5. WON Members • Experienced in clinical oncology research • All conduct NCI Cooperative Group studies • NCI R01 grant-funded research site • Vucurevich CC in Rapid City, SD • Access to cancer care for Native American populations • NCI Community Clinical Oncology Program (CCOP) • Marshfield Clinic, Green Bay Oncology, Gundersen Lutheran • NCI Community Cancer Center Program • Gundersen Lutheran, Columbia/St. Mary’s, Regional CC of Waukesha/Oconomowoc • Multiple sites have received ASCO awards

6. WON April 2006 8 members WON Sept 2011 17 members

7. Open WON Studies • Bortezomib + temsirolimus in non-Hodgkin’s lymphoma • Tim Fenske, MD, PI from Medical College of WI • Intra-pt dose escalation sorafenib in Kras positive non-small cell lung cancer • Bendamustine + rituximab in chronic lymphocytic leukemia • High dose estradiol in metastatic breast cancer • Dose dense docetaxel + cyclophosphamide in adjuvant treatment of resected breast cancer • Panobinostat in I131-refractory thyroid cancer

8. Up-coming WON Studies • Docetaxel +/- suramin in non-small cell lung cancer • Rafael Santana-Davila, MD, PI from MCW • Thoracic radiation with adaptive image guidance in limited stage small cell lung cancer • Bendamustine/rituximab/lenalinomide in chronic lymphocytic leukemia • Afatinib and paclitaxel in HER2+ metastatic breast cancer

9. Recently Completed WON Studies • Bevacizumab, lenalidomide, dex in multiple myeloma • NCI study (UWCCC funded) • Bortezomib/doxorubicin/ALCAR in multiple myeloma • Vincristine-CVAD + rituximab in mantle cell lymphoma • Bortezomib + doxorubicin/ALCAR in breast cancer • Funded by an NIH R21 • Vorinostat in non-small cell lung cancer • NCI study (UWCCC funded) • Vorinostat + bortezomib in non-small cell lung cancer • Oxali, capecitabine, and sorafenib in pancreas cancer • Lapatinib and capecitabine for colorectal cancer • Oxaliplatin, 5FU, and capecitabine in colorectal cancer • Docetaxel +/- doxercalciferol in prostate cancer

10. Correlative Assays in WON Trials • Bevacizumab, lenalidomide, dex in multiple myeloma • Specimens collected from WON sites • Plasma at baseline and through treatment • Shipped to UWCCC on dry ice • Bone marrow aspirates • Shipped to UWCCC in FedEx cold pack • Findings • Baseline MIP1α levels predicted response to therapy

11. WON • Phase II investigator-initiated heme/onc trials • Novel agents may be provided by industry or the NCI • Funding for administration of the study provided by industry, NCI grant, or UWCCC via peer-reviewed Pilot Project grant • May be developed from any site • Sites may (or may not) open any study • No minimum accrual requirement • WON is wholly funded by the UWCCC NIH Cancer Center Support Grant • UWCCC supports all aspects of conducting and regulating WON trials (1.5 FTEs) • No membership fee for local sites to join WON • WON does not receive industry support

12. WON as a Network • All sites sign an “Affiliation Agreement for the Conduct of Clinical Research” with UW Board of Regents when they join WON • This subcontract covers all activities pertaining to all WON studies, present and future • Wisconsin IRB Consortium • UW, MCW, Marshfield Clinic, Aurora Healthcare • Remaining 3 sites defer to first IRB that approved study • Encouraging other site IRBs to defer to UW IRB • Drug distribution • Either from UW Pharmaceutical Research Center or directly to WON sites from industry sponsor

13. WON as a Network • All clinical trial data are entered into UW on-line database (Oncore) and analyzed in final results • Sites receive Oncore training from UWCCC • All studies must follow UWCCC Data and Safety Monitoring Plan • UWCCC DSM Committee monitors all studies • On-site audit every 3 yrs • All accruing sites are listed as co-authors in publications • Communication • Spring and Fall half-day meetings in Madison • Educational lunch time talk by UW faculty • No registration fee to attend • Monthly conference calls • Weekly email updates

14. WON Since 1999 • 50 trials • Vast majority: industry-sponsored IITs • Others: R01, R21, NCI agent with UWCCC support • 2 have originated from MCW, 1 from Gundersen • 1141 patients enrolled • About to open our first randomized phase II study • 400 enrolled at non-UWHC sites (35%) • 16 articles in peer-reviewed journals • 23 posters or abstracts

15. J Thorac Oncol 2009;4:522-6 Chang JE, Peterson C, Choi S, Eickhoff JC, Kim K, Yang DT, Gilbert LA, Rogers ES, Werndli JE, Huie ME, McFarland TA, Volk M, Blank J, Callander NS, Longo WL, Kahl BS. VcR-CVAD induction chemotherapy followed by maintenance rituximab in mantle cell lymphoma: A Wisconsin Oncology Network study. Br J Haematol Aug 16, 2011 [Epub ahead of print].

16. WON and the Mayo Clinic Phase II Consortium (MCP2C) • WON sites may open any MCP2C study that is open at UWCCC • MCP2C is one of 9 NCI-funded consortia that studies NCI-developed drugs • Highly competitive international solicitation process • This partnership allows WON sites access to novel agents that have been evaluated by the NCI • Examples of agents/studies • Cediranib in acute leukemia and myelodysplasia • OSI-906 in breast cancer and small cell lung cancer • Veliparib and carboplatin in metastatic breast cancer

17. MN WI MD MO AZ FL Australia Mayo Clinic Phase 2 Consortium IA CO South Korea Hong Kong Singapore

18. WON: Challenges • Since the economic downturn, the pharmaceutical industry has markedly reduced financial support for investigator-initiated trials, including limiting the availability of drugs for clinical trials. • Reduced NIH/NCI funding for the CCSG • Many academic networks charge membership fees • Auditing multicenter trials • Annual virtual audit • Network-wide IRB deferral system

19. WON: Summary • Highly collegial, efficient, motivated, experienced clinical trial network that extends state-of-the-art oncology research throughout the state • Growing membership, increasing rate of accrual • Randomized phase II trials possible • Four largest members defer to single IRB (WIC) • Drug distribution by UW Pharmacy • On-line clinical data entry and analyses • Collection of specimens for correlatives possible • Data and safety monitoring plan in place • We need more novel drugs to study