Clinical Trials – An Academic Perspective Mohammed Milhem, MD University of Iowa

General 3 % of adult cancer patients nationwide enroll in clinical trials each year Advances in cancer treatment depend on clinical trials Barriers to treatment are both patient related and physician related

University of Iowa Last year saw 3,274 new cancer patients 278 cancer patients were placed on treatment clinical trials Accrual rate 8.5% Clinical Trials Support Core supports 21 oncologists Still not enough

Academic Centers—Expectations Investigator initiated trials Capabilities of translational research Capacity for a phase I, II, III trials Access to diverse group of patients Access to complex patients Access to National Groups

Limitations—Funding A recent survey of 122 major academic medical centers in the US revealed that 79% of all clinical trials were sponsored by private industry, and 76% of funding for clinical investigations came from private, for-profit companies It is unlikely that this trend of increasing industry-supported clinical research will reverse or even slow down Slow process to get trial up and running

Clinical Trial Approved by Investigator Investigator initiated Industry National Clinical Trials Support Core Office Contract Office Sponsored Programs PRMC IRB Study Open For Accrual TIME === 4-6 months Clinical Trials Radiation Committee

PRMC Peer Review and Monitoring Committee Once a month meeting 10 trial limit, first come first serve Cooperative group studies undergo an administrative meeting Industry and investigator initiated undergo a scientific meeting Investigator initiated trials take the longest time

Sarcoma Related Trials Rare tumor-need of a centralized system Last year no sarcoma trials, no patients accrued on trials University of Iowa joins SARC 2 clinical trials obtained from this national group currently open at the University 2 industry sponsored trials open and actively accruing patients 1 Cancer Center supported investigator initiated trial for sarcoma tissue banking

Clinical Studies 4 Open studies. 3 clinical 1 collection study 3 Pending studies 2 Studies under consideration 2 Pediatric trials open for bone sarcomas 1 Study on hold ARIAD= 4 pts Yondelis= 1pt SARC 006= 0 pt

Clinical Research Program Study TitleStatus OPEN STUDIES ARIAD A Pivotal Trial to Determine the Efficacy and Safety of AP23573 when Administered as Maintenance Therapy to Patients with Metastatic Soft-Tissue or Bone Sarcomas Approved and open to accrual. SARC 006 Phase 2 trial of chemotherapy in sporadic and NF type 1 associated with high-grade unresectable MPNST Approved and open to accrual. AT IRB Schering Plough Study to determine activity of SCH in subjects with osteosarcoma or Ewing's than has relapsed after standard therapy Submitted to WIRB 9/23/08. Awaiting review. SARC 009 A Phase II Trial of Dasatinib in Advanced SarcomaWaiting for final PRMC approval, then study will be scheduled for IRB meeting. Pfizer A Phase IIIB Randomized, Active Controlled Open-Label Study of Sunitinib 37.5 mg daily vs. Imatinib Mesylate 800 mg daily in the treatment of Patients with GIST who have had progressive disease while on 400 mg daily of Imatinib Have protocol. On HOLD Pfizer A Randomized Phase II Open Label Trial of Sunitinib Malate vs Imatinib Mestlate in the First Line Treatment of Patients with Unresectable or Metastatic Malignant GIST Pfizer put this study on hold for now.

System Barriers Slow process ~ not efficient High start up fees Meet more frequently is difficult Need more reviewers for the PRMC More clinical trial support core employees ? Is It faster in the private sector ? Investigator initiated trials

Barriers ~ Patient Related Issues Logistic factors such as driving distance or time demands Concerns about being treated at a university center and of losing continuity with their primary oncologist The relationship with their primary oncologist was of very high importance to elderly patients

Physician-Related Barriers The potential presence of co-morbid conditions aside from those excluded by the protocol Anticipating that older patients would have difficulty understanding the requirements of a clinical trial The logistics and time involved in enrolling older patients onto clinical trials

Barriers to Minority Group Participation in Cancer Clinical Trials  Mistrust-confusion between medical care and research  Lack of awareness  Lack of invitation  Cultural beliefs  Eligibility criteria/comorbid conditions  Cost/lack of insurance  Language/linguistic differences  Physician lack of awareness Intercultural Cancer Council. Cancer Clinical Trials: Participation by Underrepresented Populations

Barriers to True Voluntary Participation Desire on the part of patient to please a family member or physician A feeling by the patient that no other options exist Perceptions by patients that they are required to be in clinical trial

Solutions Providing more information about trials to the community oncologists as well as the prospective enrollees Creating more supportive systems to help patients navigate the complex terrain leading to a clinical trial especially for elderly patients Mechanisms to facilitate the ability of the primary oncologist to deliver such a trial via a network approach-constant communication Experience with SARC as a national program for being a designated site

Solutions Another potential mechanism for enhancing enrollment, and one certainly consistent with the overall goals of oncology, would be to seek treatments that have a higher therapeutic-to- toxicity ratio Oral medications, easier to give, better models. Example: ARIAD maintenance study Trials that are easy to administer, require less frequent visits and are not cumbersome for the patient Actively engage with the patient on trial to help maintain the trust

Better Utilization of Resources Select trials that have been open for a while Don’t try to open every trial Open trials for different tumor populations and at different stages of their disease ( complimentary) Continually assess trial status – if not accruing close it Replace trials that accrued well, as this is serving an active population Co-ordinate in network the opening of trials

Thank You Grant Wood Fall Plowing