How to Get a Trial in a Cooperative Group

1
How to Get a Trial in a Cooperative Group
ASCO/AACR Workshop on Methods in Clinical Cancer
Research Vail, CO August 2007

• Neal J. Meropol
• Fox Chase Cancer Center

2
Audience Response 1Cooperative Groups are only
for people with gray hair, or no hair at all.

• True
• False

3
What is a Cooperative Group?

• Clinical Trials Cooperative Groups established in
  1955
• NIH U10 cooperative agreement (assistance
  rather than acquisition mechanism) compete
  every 6 years
• Major emphases
• definitive studies or preparatory efforts for
  these studies
• combined modality approaches
• translational research, correlating biologic
  insights gained from the laboratory with disease
  behavior and treatment outcome
• Goals Improve therapy, Adjunct studies, Cancer
  Control, Clinical trials methodology
• 20,000 patients enrolled annually 90M annual
  budget

4
Cooperative Group Structure

• Three required components headquarters,
  statistical/data management center,
  investigators/institutions
• Four main type disease (e.g. GOG), modality
  (e.g. RTOG), expertise (e.g. COG), multiumodality
  (e.g. ECOG)
• Examples ACOSOG, AMCTC, SWOG, RTOG, GOG, NCCTG,
  CALGB, ECOG, CCTG, COG, NSABP

5
Disease vs. Modality Committees

• Disease Committees
• the driver of phase III trials
• Included as components of the U10 grant
• Not all types of cancer are represented in every
  group
• Modality Committees
• Vary by group
• May stand alone or be embedded in operations
  portion of U10 grant
• May play supportive role or conduct studies
• Examples surgery, radiation, developmental
  therapeutics, pathology/laboratory science
• Cross individual disease barriers

6
Developmental Therapeutics Committees

• May spearhead studies or conduct correlatives
  embedded in other trials
• Pharmacogenetics
• Population pharmacology
• New drug development
• Disease-independent correlatives
• Orphan diseases
• Special populations
• Organ dysfunction, elderly

7
Audience Response 2The best resources that a
Cooperative Group has to offer me are

• Patients for clinical trials
• Banked biologic specimens for correlative
  research
• Clinical databases for retrospective study
• Access to thought leaders for mentorship and
  professional advancement

8
How to break in

• Note Cooperative Group leadership is dependent
  upon young investigators, and notices talent
• Write a letter to introduce yourself to the group
  and committee chair
• Have your mentor do the same your local mentor
  can help by continuing to bring your name forward
• Make an appointment to meet with the committee
  chair at the next group meeting
• Contribute to discussion at meetings be visible
• Volunteer to write up old data
• Pitch concepts dont forget about archival
  tissue and data
• Written and oral presentations should be more
  complete and polished than those of established
  investigators

9
The Players at Macro Level
Intergroup
Cooperative Group
Concept level
CTEP
Industry
Protocol level
FDA
CTSU
CIRB
10
The Relationship with Industry

• The public system is dependent upon industry
  support
• Pharma not only supplies drug it is a major
  support mechanism for correlative science and
  increasingly for administrative costs (
  accrual)
• CRADAs (cooperative research development
  agreements) mandate dual sign-off
• Find shared goals
• Recognize your value and that of your industry
  partner

11
So you have an idea..
12
Where do you shop this concept?

• Disease committee chair
• Disease committee core members
• Your cooperative groups executive committee
• NCI disease Task Force
• NCI disease Steering Committee
• Cancer Therapy Evaluation Program (CTEP)
• Then, write a protocol.

13
NCI Steering Committees and Task Forces

• Implemented in response to NCI Clinical Trials
  Working Group report regarding conduct of phase
  III clinical trials
• Effort to ensure involvement of all
  constituencies, including those not participating
  in cooperative groups (e.g. RO1 investigators,
  SPORE investigators)
• Effort to improve coordination, reduce redundancy
• Effort to streamline ultimate NCI review, by
  beginning CTEP involvement earlier in the
  development process

14
Example Gastrointestinal Cancer
GI Steering Committee -Chairpersons -Coop Group
GI Chairs -CTEP -Stats -Lab investigators -R01/SPO
RE investigators -Advocates
TASK FORCES
Esophagogastric
Anal-Rectal
Neuroendocrine
Hepatobiliary
Colon
Pancreas
15
Timelines
16
Process Flow Map CALGB(Dilts, Sandler, Baker et
al. JCO, 2006)
17
Calendar Day per Step CALGB(Dilts, Sandler,
Baker et al. JCO, 2006)
18
What can you do to keep the process moving?

• Get to know the protocol development team
• Respond rapidly to requests
• Keep an eye on the process
• Ask how you can help
• Stay in touch with the contract team

19
Barriers to Success of Cooperative Phase III
Trials

• Note most accrual comes from community
  oncologists the ivory tower does not represent
  reality
• Cooperative Group studies are not adequately
  reimbursed and cost the investigator money
• Correlative study participation may not receive
  appropriate credit/reimbursement
• Competition from industry trials
• The system is heavily dependent on volunteerism

20
Key Criteria for a Successful Study

• Keep it simple
• Ask an important clinical question
• Ask one clinical question
• Use a treatment that cant be obtained outside of
  a trial
• Involve patient advocates in design and beyond
• Design a marketing strategy early, and implement
  early and often

21
Example of a Doomed Study E3201

• At the time of design, standard adjuvant therapy
  for rectal cancer
• Either pre-op or post-op radiation
• Post-op chemotherapy
• Standard chemotherapy was 5-FU
• Colon adjuvant studies with irinotecan and
  oxaliplatin not reported

22
E3201
23
E3201 What Happened?

• Poor accrual
• Considerations
• Complex design
• FOLFOX works in colon adjuvant setting
• FOLFIRI data in colon adjuvant setting pending
• Most practitioners prefer neoadjuvant therapy
• Theres no cool drug in the study

24
E3201 Revision Proposal
/- bevacizumab
25
E5204 Trial Schema
Target accrual 2100 patients
Arm I mFOLFOX6 q2w x 12
RANDOM I Z E
Stratify ECOG PS (0 or 1) Clinical staging
Prior oxaliplatin Prior chemoradiation therapy
Arm II mFOLFOX6 bevacizumab q2w x 12
Patients who received prior neoadjuvant
oxaliplatin on protocol NASBP-R-04 receive up to
9 courses of treatment followed by 3 additional
courses of leucovorin calcium IV and
fluorouracil IV with (Arm II) or without (Arm I)
bevacizumab for up to 3 courses.
26
Key Criteria for a Successful Study

• Keep it simple
• Ask an important clinical question
• Ask one clinical question
• Use a treatment that cant be obtained outside of
  a trial
• Involve patient advocates in design and beyond
• Design a marketing strategy early, and implement
  early and often

27
Audience Response 3The most important
attribute I require to be successful in breaking
into a Cooperative Group is

• Good ideas
• Strong mentor/advocate
• Compelling preliminary data
• Charm
• My center is a major accrual site
• Patience and perseverance

28
Why conduct cooperative group research?

• Personal
• You get to visit cool places and stay in nice
  hotels ...not
• National platform with thought leaders
• Access to infrastructure and patient resources
  tissue and data, not merely patients

• Institutional
• Cancer Center Support Grant credit
• Coop Group credits
• notoriety

• Societal
• Address key clinical questions
• Minimize potential for industry bias in design,
  conduct, reporting
• Public ownership of data

29
(No Transcript)