Clinical Trials

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Clinical Trials An Academic Perspective

• Mohammed Milhem, MD
• University of Iowa

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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

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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

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Academic CentersExpectations

• 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

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LimitationsFunding

• 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

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

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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

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Clinical Studies
ARIAD 4 pts

• 4 Open studies.

3 clinical
Yondelis 1pt
SARC 006 0 pt
1 collection study

• 3 Pending studies
• 2 Studies under consideration
• 2 Pediatric trials open for bone sarcomas
• 1 Study on hold

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Clinical Research Program
  Study Title Status
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.
OPEN STUDIES 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 SCH717454 in subjects with osteosarcoma or Ewing's than has relapsed after standard therapy Submitted to WIRB 9/23/08. Awaiting review.
AT IRB SARC 009 A Phase II Trial of Dasatinib in Advanced Sarcoma Waiting for final PRMC approval, then study will be scheduled for IRB meeting.
Pfizer A6181112 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 6181155 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.
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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

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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

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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

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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 http//iccnetwork.org/cancerfacts/cfs1
1.htm
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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

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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

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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-toxic
  ity 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

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Better Utilization of Resources

• Select trials that have been open for a while
• Dont 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

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Thank You
Grant Wood
Fall Plowing
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