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S0820
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S0820
A double blind placebo-controlled trial
of Eflornithine and Sulindac to prevent
recurrence of high risk adenomas and
second primary colorectal cancers in
patients with Stage 0-III Colon Cancer,
Phase III.
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Study Coordinators
Jason A. Zell, D.O., M.P.H. (Medical Oncology)
UC Irvine Medical Center
Powel H. Brown, M.D., Ph.D. (Medical Oncology)
M.D. Anderson Cancer Center
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Primary Objective
Assess whether eflornithine (+/- sulindac),
sulindac (+/- eflornithine) or the
combination are effective in reducing the
three-year event rate (high-risk adenomas
and second primary colorectal cancers) in
patients with previously treated Stage 0-III
colon cancer.
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U.S. Cancer statistics, 2013
CA: A Cancer Journal for Clinicians
Volume 63, Issue 1, pages 11-30, 17 JAN 2013 DOI: 10.3322/caac.21166
http://onlinelibrary.wiley.com/doi/10.3322/caac.21166/full#fig1
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Colorectal Cancer
• Primary Prevention: Screening
and early detection result in 5year survival rates of 90%
(colon) and 80% (rectum) for
localized disease
• Result: overall survival is 64%*
5-year Survival (%)
• The problem: 50-60% receive
proper screening, and 60%
present with advanced stage
disease
Survival
Estimates
Siegal, R, Ca-A Cancer Journal for
Clinicians 2013; 63 (1):11-30.
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Second Primary Colorectal Cancers
among Stage I-III CRC cases
• Occur in ~1-4% of treated
CRC patients
• Among 69,809 colon
cancer cases in California
1990-2005, 40% increased
risk of 2nd primary CRC
among CRC cases
compared to the underlying
population at risk*
• Standardized Incidence Ratio
= 1.4 (95% CI 1.3-1.5)
* Raj, KP, et al. Risk of second primary colorectal cancer among colorectal cancer
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cases: A population-based analysis. Professional
J Carcinogenesis
2011;10:6Version 02 201409
Accrual Targets
Sex/Gender
Ethnic Category
Females
Males
Total
Hispanic or Latino
32
+
44
76
Not Hispanic or Latino
608
+
804
1,412
Ethnic Category: Total of all subjects
640
+
848
=
1,488
American Indian or Alaskan Native
9
+
13
=
22
Asian
19
+
26
=
45
Black or African American
51
+
68
=
119
Native Hawaiian or other Pacific Islander
9
+
13
=
22
White
552
+
728
=
1,280
Racial Category: Total of all subjects
640
+
848
=
1,488
Racial Category
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S0820 Study Design:
(n=1488)
R
E
G
I
S
T
E
R
S
T
R
A
T
I
F
Y*
R
A
N
D
O
M
I
Z
E
Baseline data *Stratification
collection,
by stage
audiogram,
blood, CTscans, &
colonoscopy at
Year-1 post
resection
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5-year
follow
-up
3-year study
intervention
eflornithine +
sulindac placebo
(n=335)
eflornithine placebo +
sulindac
(n=335)
eflornithine +
sulindac
(n=335)
eflornithine placebo +
sulindac placebo
(n=335)
Colonoscopy
Primary
endpoint =
3-year rate
of high risk
adenomas
or 2nd
primary
CRCs.
End-of-study
audiogram,
blood collection
Activated: March 1, 2013
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F
O
L
L
O
W
U
P
Study Drug Information
 Eflornithine (DFMO) or Placebo, 250 mg,
2 tablets oral daily x 3 years
 Sulindac (NSAID) or Placebo, 150 mg,
1 tablet oral daily x 3 years
~1,488 volunteers assigned randomly to one of
four trial arms
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take 2
take 1
Arm 1
placebo
placebo
Arm 2
eflornithine
placebo
Arm 3
placebo
sulindac
Arm 4
eflornithine
sulindac
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Cardiovascular Risk Amended
As of May 1, 2014, the protocol was amended to define specific
cardiovascular risk factors and specific blood pressure parameters for
eligibility. Patients must NOT have:
- uncontrolled high blood pressure
- unstable angina
- history of documented myocardial infarction
- history of document cerebrovascular accident
- Class III or IV heart failure as defined by the NY Heart Association
- known uncontrolled hyperlipidemia within last 3 years
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Eligibility
• Stage 0, I, II or III colon adenocarcinoma treated per standard
care with resection alone or in combination with adjuvant
chemotherapy
• Adjuvant chemotherapy must have been completed at least
30 days prior to registration
• Patients with rectosigmoid cancers are eligible only if their
treatment did NOT involve radiation therapy (i.e. neo-adjuvant
or adjuvant radiation) (mid-low rectal cancers are not eligible)
• Patients must be registered between 274 days and 465 days
(inclusive) of primary resection
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Eligibility (continued)
• CT scan performed at least 180 days after colon resection
• Must be at least 18 years of age & no history of familial
adenomatous polyposis, hereditary nonpolyposis colorectal
cancer, or inflammatory bowel disease
• Must have a pure tone audiometry evaluation to document
air conduction
• Not be expecting to receive radiation or additional
chemotherapy
• Not be receiving or plan to receive concomitant
corticosteroids NSAIDs, nor anticoagulants on a regular or
predictable intermittent basis
• Patients must have adequate blood counts
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Follow-up
• Year 1: H & P, CBC & chemistries every 3 months
• Year 2 & 3: H & P, CBC & chemistries every 6 months
• PE & chemistries, colonoscopy & pure tone audiogram 3 years
after randomization
• Patients followed annually for 5 years (after completion of 3
years of intervention):
• H&P
• Weight and Performance Status
• Follow-up colonoscopy at 8 years post-registration per NCCN
guidelines
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Adherence
•
•
•
•
Study drug adherence measured by returned tablet count
Unused medication returned to the clinic at each visit
Patients document study drug intake on an Intake Calendar
Individualized adherence strategies used if adherence
is ↓75%:
•
•
•
•
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Communicate with patient to define barriers
Review patient’s routine for taking study drugs
Seek family assistance
Consider more frequent contact with patient using phone check-in
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Primary Endpoint
• 3-year event rate after registration among Stage
0-III colon cancer patients
• Event = high risk adenoma or 2nd primary colorectal
cancer
• High risk adenoma = either advanced adenoma
(villous or tubulovillous histology, size ≥ 1 cm, or high
grade dysplasia) or multiple adenomas (3 or more each
> 0.3 cm)
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Secondary Endpoints
•
•
•
•
•
•
•
•
•
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Total advanced colorectal event rate
Recurrence
High-grade dysplasia
Adenomas with villous features
Adenomas ≥ 1 cm
Multiple adenomas
Adenoma
Total colorectal event rate
Time to first clinically apparent high-risk adenoma or 2nd
primary colorectal cancer
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Optional for patients…….
• Submission of blood specimen for nutritional assays and
banking:
• including genotyping and biochemical assays
• fasting whole blood sample required after registration and prior
to beginning treatment
• Diet and Lifestyle Substudy:
• completion of Diet & Lifestyle Questionnaires after registration
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Pharmacokinetic Study
ALL SITES have the option to participate in the population
pharmacokinetic sampling:
• Sampling occurs twice at 3 & 12 months during morning visits
• Collected only on patients receiving intervention at 3 & 12
months
• Kits are ordered from Cancer Prevention Pharmaceuticals, Inc.
Interested sites should contact:
Patricia O’Kane [email protected]
SWOG Operations Office
San Antonio, TX
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Please help identify potential patients
History of stage 0, I, II or III colon adenocarcinoma
Treated with resection alone or in combination with adjuvant
chemotherapy
NED at one year post-operative assessment
Timing:
 Patients must be registered between 274 and 465 days (inclusive) of primary
resection
 Colonoscopy and CT scans of chest, abdomen and pelvis NED performed at least
274 days after resection date and prior to registration
 Polyps detected at colonoscopy must be completely removed
 Adjuvant chemo completed ≥ 30 days prior to registration
 CT Scan is for high risk patients per NCCN guidelines & at discretion of
treating physician
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S0820 Web Page
Recruitment Materials available:
• Printable Brochure
• Professional Slide Set
• Promotional Flyers
• Promotional Letter to Physicians
• Strategies
• Study Logo and Printing Instructions
Materials for the Investigators and Staff include:
• Thank You letter to Referring Physicians
• Webinar
• Adherence Strategies
• FAQs
• Pocket Protocol
Materials for the patient include:
• Thank You Letter from the PI for Enrolling
• List of Resources
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Thank You
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