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Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk

Phase 2
18 Years
Open (Enrolling)
Adenomatous Polyp, Colorectal Cancer, Precancerous Condition

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Trial Information

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.

Inclusion Criteria:

- History of any size adenoma, known adenoma on present exam, or colon cancer within
the last 6 years

- Scheduled for colonoscopy

- Ability to understand and the willingness to sign a written informed consent document

- Willingness to forego PEG laxative during the study period; if the patient has been
on a consistent dose of non-PEG laxative for 90 days prior to study entry, the
participant may continue those laxatives; participants must agree to restrict
additional laxative use to the rescue medication (bisacodyl) provided

- ECOG performance status 0-1 (equivalent to Karnofsky >= 70%)

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- INR =< 1.5

- Total bilirubin =< 1.5 X institutional ULN

- AST (SGOT)/ALT (SGPT) =< 1.5 X institutional ULN

- eGFR > 45

- BUN < 40

- Women of child-bearing potential must agree to use adequate contraception (hormonal
or barrier method of birth control; restricting intercourse to a surgically
sterilized partner; abstinence) for the duration of study participation; should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her study physician immediately

- If patients are on a dose of cardioprotective aspirin, they must have been on a
stable dose for three months prior to colonoscopy and agree to remain at that dose
for the six months duration of the study; in addition, patients must agree to limit
therapeutic NSAID use (e.g. pain relief) to no more than 30 cumulative days during
the six month duration of the trial

Exclusion Criteria:

- Average of > 2 bowel movements per day for the 90 days preceding study entry as
assessed by self-report at baseline

- Average consistency of stools described as watery or loose for the 90 days preceding
study entry as assessed by self-report at baseline

- Systemic chemotherapy for any cancer within 18 months prior to enrollment or evidence
of active malignant disease

- Radiation to the rectum within 24 months prior to enrollment

- Polyethylene glycol use within 3 months of enrollment (except as part of colonoscopy

- Systemic corticosteroid use

- Anticoagulant therapy

- Inflammatory Bowel Disease

- Removal of the rectum

- Evidence of proctitis (radiation, IBD, infectious, etc.) by history or endoscopy

- Other investigational agent use within 30 days prior to enrollment

- History of adverse reactions attributed to compounds of similar chemical or biologic
composition to polyethylene glycol, bisacodyl or methylene blue

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnancy

- Patient must not have used suppository medication or enemas for the three months
prior to the trial or for the duration of the trial except as directed for
colonoscopy or flexible sigmoidoscopy procedure bowel preparation

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Difference A-B (After treatment minus Before treatment) of EGFR expression

Outcome Description:

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.

Outcome Time Frame:

Up to 6 months

Safety Issue:


Principal Investigator

Raymond Bergan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University


United States: Food and Drug Administration

Study ID:




Start Date:

January 2013

Completion Date:

Related Keywords:

  • Adenomatous Polyp
  • Colorectal Cancer
  • Precancerous Condition
  • Colorectal Neoplasms
  • Precancerous Conditions
  • Adenomatous Polyps



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