Transcript Title of Presentation - UW Department of Family Medicine

Wisconsin
Oncology
Network (WON)
Anne Traynor, MD
UWCCC Heme Onc
[email protected]
Mary Beth Wims
Lynn Volk
UWCCC Central Research Office
[email protected]
[email protected]
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.
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
WON Members
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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
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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
• 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
WON
April 2006
8 members
WON
Sept 2011
17 members
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
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
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
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
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
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
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
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
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].
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
Mayo Clinic
Phase 2 Consortium
MN
WI
MD
IA
CO
MO
AZ
FL
Australia
South Korea
Hong Kong
Singapore
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
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
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– 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