Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk
I. To evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8g or 17g/day
for six months) versus placebo on EGFR expression.
I. To determine the effect of PEG 3350 on aberrant crypt foci (ACF) number. An exploratory
comparison between the reduction in ACF number between the low dose (8g PEG 3350 / day) and
higher dose (17g PEG 3350 / day) groups.
II. To determine the effect of PEG 3350 on mucosal epithelial proliferation (Ki-67).
III. To determine the effect of PEG 3350 on mucosal apoptosis (cleaved caspase-3).
IV. To determine the effect of PEG 3350 on SNAIL protein expression. V. To determine the
effect of PEG 3350 on mRNA expression of SNAIL and EGFR.
OUTLINE: is a multicenter study. Patients are stratified according to recruitment site and
number of aberrant crypt foci (ACF) (> 20 vs 11-20 vs 5-10). Patients are randomized to one
of three treatment arms.
ARM I: Patients receive low-dose polyethylene glycol orally once daily.
ARM II: Patients receive high-dose polyethylene glycol orally once daily.
ARM III: Patients receive placebo (i.e., maltodextrose powder) orally once daily.
In all arms, treatment begins within 6-10 days after colonoscopy and continues for up to 6
months in the absence of unacceptable toxicity.
Patients undergo flexible sigmoidoscopy at baseline (during prestudy colonoscopy) and at
completion of study treatment. Patients undergo biopsies of normal mucosa (i.e., at least 1
cm from an ACF) and ACF sites (if present) to obtain tissue for evaluation of treatment
response and tissue biomarkers. Tissue samples are assessed for cleaved caspase-3, Ki-67,
and SNAIL by IHC and for EGFR and E-cadherin expression by Western blot. Samples are also
analyzed for mRNA expression of EGFR and SNAIL by RT-PCR. Blood samples are collected
periodically for RNA isolation.
After completion of study treatment, patients are followed at 30 days.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Difference A-B (After treatment minus Before treatment) of EGFR expression
The difference in the observed change from baseline in each treatment arm will be compared with placebo. EGFR will be measured by immunoblot. mRNA expression of EGFR will be measured by RT-PCR.
Up to 6 months
United States: Food and Drug Administration
|Boston Medical Center||Boston, Massachusetts 02118|
|Northwestern University||Chicago, Illinois 60611|
|University of Chicago||Chicago, Illinois 60637|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|