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IDEA Update
International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Colon Cancer Prospective Pooled Analysis
A newsletter for IDEA investigators
Trial Profile
Cancer and Leukemia Group B
(CALGB)/Southwest Oncology
Group (SWOG) C80702 Trial
Profile
The C80702 trial is coordinated by
the Cancer and Leukemia Group B
(CALGB) and the Southwest
Oncology Group (SWOG), and
funded by the National Cancer
Institute. C80702 is the only
current, randomized phase III
trial in the United States for
patients with completely resected
stage III colon cancer. The trial
has a 2x2 factorial design, with
patients randomized to three
years of celecoxib or placebo and
6 or 12 treatments of adjuvant
chemotherapy with FOLFOX.
Patients are randomized in a 1:1
ratio for each of the treatment
arms (6 versus 12 treatments
and celecoxib versus. placebo).
Stratification is done for the
number of involved lymph nodes
(1-3 versus 4 or more) and for
regular low-dose aspirin use.
March 2011
Accrual Update
PRODIGE-Groupe Coopérateur
Multidisciplinaire en Oncologie
(GERCOR) trial
Activation date: May 2, 2009
Current status: Active, recruitment
ongoing
Planned accrual: 2,000 patients
Sites open: 125 open centers
(96 with at least one patient)
Current accrual: 531 patients
(all stage III disease)
Other activity: Amendment related
to XELOX is being submitted to
authorities
Short Course Oncology Treatment
(SCOT) trial
Activation date: March 27, 2008
Current status: Open in the U.K.
and Australia
Planned accrual: 9,500 patients
Sites open: 179 centers open in
U.K./Australia (163 centers have
at least one patient enrolled)
Current accrual: 1,877 patients
(112 in January 2011 – record
month for SCOT)
Other activity: Other centers from
Denmark, Austria, Qatar, India
and Spain are interested in
participating in SCOT
Cancer and Leukemia Group B
(CALGB)/Southwest Oncology Group
(SWOG) trial C80702
Activation date: July 2010
Current status: Open
Planned accrual: 2,500 patients
Sites open: 588 sites
Current accrual: 97 patients
Three of Six Colon Adjuvant
(TOSCA) trial
Activation date: First patient
enrolled on June 20, 2007
Current status: Open
Planned accrual: 2,860 to 4,100
patients
Sites open: 138 sites
Current accrual: 2,222 patients
Hellenic Oncology Research
Group (HORG) trial
Activation date: October 2010
Current status: Open
Planned accrual: 1,000 patients
Sites open: 15 sites have been
activated (13 centers have at least
one patient enrolled)
Current accrual: 105 patients
(32 with high-risk stage II
disease, the remaining 73
with stage III disease)
continued on next page
IDEA Steering Committee: Jim Cassidy, M.D., principal investigator (P.I.), Short Course Oncology Treatment (SCOT) trial; Jim Paul, M.S.,
SCOT trial; Roberto Labianca, M.D., co-P.I., Three of Six colon adjuvant (TOSCA) trial; Alberto Sobrero, M.D., co-P.I., TOSCA trial;
Jeffrey Meyerhardt, M.D., M.P.H., Cancer and Leukemia Group B (CALGB) chair, C80702 trial; Anthony Shields, M.D., Ph.D., P.I., Southwest
Oncology Group (SWOG), C80702 trial; Thierry André, M.D., co-P.I., PRODIGE-Groupe Coopérateur Multidisciplinaire en Oncologie
(GERCOR) trial; Julien Taieb, M.D., co-P.I., PRODIGE-GERCOR trial; Axel Grothey, M.D., North Central Cancer Treatment Group (NCCTG)
Secretariat; Daniel Sargent, Ph.D., NCCTG Secretariat; Ioannis Souglakos, M.D., P.I., Hellenic Oncology Research Group (HORG).
IDEA Coordination Committee: Donna Niedzwiecki, Ph.D., (CALGB); Irene Floriani, Ph.D., (TOSCA), Jim Paul, M.S., (SCOT);
Frank Bonnetain, Ph.D., (GERCOR-PRODIGE); and Daniel Sargent, Ph.D., (Secretariat).
continued from page 1
The primary study objective is to compare the three year diseasefree survival (DFS) in patients receiving FOLFOX versus FOLFOX
plus celecoxib. The study is powered to detect a hazard ratio of
0.79 favoring celecoxib, which corresponds to an increase in the
probability of being disease-free at three years from 72 percent to 78
percent.
The secondary study objective is to contribute to the International
Duration Evaluation of Adjuvant Chemotherapy (IDEA) colon
cancer prospective pooled analysis of patients receiving 6 versus 12
treatments of adjuvant FOLFOX chemotherapy, examining DFS and
overall survival (OS). Other trial objectives include comparing the OS
in patients on celecoxib versus placebo, and assessing the toxicities
of celecoxib, and the toxicities of celecoxib and the two duration
schedules of FOLFOX.
Companion research include correlative science
studies to:
• Assess molecular features within the tumor that influence the
efficacy of therapy
• Assess baseline plasma 25(OH)-vitamin D levels, mRNA
expression signatures
• Assess the role of genetic variations in cyclooxygenase and related
pathways
The trial will also identify single nucleotide polymorphisms (SNPs)
and copy number variations associated with toxicity and DFS. The
influence of diet and lifestyle habits will also be examined in relation
to DFS.
Jeffrey Meyerhardt,
M.D., M.P.H.
Anthony Shields,
M.D., Ph.D.
Jeffrey Meyerhardt, M.D., M.P.H., at the
Dana-Farber Cancer Institute, Harvard Medical
School, Boston, and Anthony Shields, M.D.,
Ph.D., at the Karmanos Cancer Institute, Wayne
State University, Detroit, are the study co-chairs.
In addition to CALGB and SWOG, the trial has
been endorsed by the North Central Cancer
Treatment Group (NCCTG), Eastern Cooperative
Oncology Group (ECOG) and National Cancer
Institute of Canada (NCI-C).
This trial opened in July 2010 and 97 patients
are enrolled to date. The trial is now open at 588
centers and are in the process of approving the
trial. Once all centers have activated the trial, the
target monthly accrual is 66 patients and total
planned accrual is 2,500 patients.
News/Updates
Coming soon: IDEA stage II
At the last IDEA steering
committee meeting, the group
noted that several of the trials
in IDEA include patients with
high-risk stage II disease.
This was recognized as an
opportunity for the IDEA
collaborators to implement a
prospective pooled analysis of
the stage II patients. The IDEA
coordinating committee, which
includes the statisticians from
each trial, is drafting a plan for
the stage II pooled analysis for
review by the IDEA steering
committee. This analysis will
likely occur after the primary
IDEA stage III analysis,
and will provide additional
valuable information about
stage II colon cancer.
Fifth IDEA trial opens
At the fall 2010 IDEA steering
committee meeting, the group
voted to officially include a
fifth trial in IDEA. The new
trial is being conducted by the
Hellenic Oncology Research
Group (HORG), with Ioannis
Souglakos, M.D., serving as
principal investigator. The
trial opened in fall 2010 and
planned accrual is 1,000
patients. Further details on
this trial will be included in an
upcoming IDEA newsletter.
IDEA Overview
The purpose of International Duration Evaluation
of Adjuvant Chemotherapy (IDEA) is to facilitate
the collaboration among multiple individual trials
conducted around the world for a single, pooled
analysis of the primary aim: To test whether 3 months
of oxaliplatin-based adjuvant therapy is non-inferior
for disease-free survival (DFS) to 6 months of the
identical therapy in patients with stage III colon
cancer.
The IDEA Steering Committee is comprised of 2
members from each group coordinating an individual
trial, plus 2 members from a Secretariat, North
Central Cancer Treatment Group (NCCTG), who are
responsible for coordinating the data pooling and the
joint analysis. (See list on page 1.) Members of IDEA
have agreed to pool the data from their individual
trials to allow a definitive analysis consisting of
at least 10,500 patients, using DFS as the primary
endpoint. Non-inferiority will be declared if the
2-sided 95 percent confidence interval for the hazard
ratio comparing 3 to 6 months of therapy lies entirely
Contact
information
below 1.10. A sample size of 10,500 patients provides
90 percent power, based on an expected accrual
duration of 3.5 years, 3 years minimum follow-up, and
an expected 3-year DFS rate in the control group of 72
percent to declare non-inferiority if the true hazard
ratio is 1.0.
Individual trials included in IDEA may address
additional trial-specific hypotheses in a factorial
design; the analyses of these additional hypotheses
will be trial specific and not involve IDEA. The IDEA
pooled analysis will consist only of stage III colon
cancer patients enrolled in these trials. Only patients
randomized to 3 or 6 months of a FOLFOX regimen
(FOLFOX4 or mFOLFOX6) or XELOX will be included
in the pooled analysis. The trials in IDEA share
accrual information on an ongoing basis (at least every
6 months). The final pooled analysis will be conducted
jointly by the IDEA Steering Committee, with the
Secretariat and main data analysis site at Mayo Clinic/
NCCTG. Currently, 5 trials in IDEA are actively
enrolling patients.
For further information on IDEA, contact the NCCTG Secretariat at:
NCCTG Operations Office
200 First Street S.W.
Rochester, Minnesota 55905
E-mail: [email protected]
MC4094-01rev0311