Polyethylene Glycol 3350 in Preventing Cancer in Patients at Risk of Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00828984
First received: January 23, 2009
Last updated: July 22, 2014
Last verified: April 2014
  Purpose

This randomized phase II trial studies how well polyethylene glycol 3350 works in preventing cancer in patients at risk of colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of polyethylene glycol 3350 may stop cancer from growing in patients who are at risk of colorectal cancer. It is not yet known which treatment regimen is more effective in preventing colorectal cancer.


Condition Intervention Phase
Adenomatous Polyp
Colorectal Cancer
Drug: polyethylene glycol
Other: placebo
Procedure: colonoscopy
Procedure: sigmoidoscopy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Difference A-B (After treatment minus Before treatment) of EGFR expression [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Changes in ACF count, Ki-67 (proliferation), activated caspase-3 (apoptosis), SNAIL and E-cadherin as measured in endoscopically normal (non-ACF) mucosal biopsies [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    Ki-67, activated caspase-3, and SNAIL will be measured by IHC. EGFR and E-cadherin will be measured by immunoblot. mRNA expression of EGFR and SNAIL will be measured by RT-PCR.


Estimated Enrollment: 140
Study Start Date: October 2009
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (low-dose polyethylene glycol)
Patients receive low-dose polyethylene glycol PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.
Drug: polyethylene glycol
Given PO
Other Names:
  • PEG
  • Poly(oxyethylene)
  • Polyethylene Glycol 400
  • Polyethylene Glycol 8000
  • Polyethylene Oxide
Procedure: colonoscopy
Patients undergo diagnostic procedure
Other Name: colonoscopic studies
Procedure: sigmoidoscopy
Patients undergo diagnostic procedure
Other Name: Proctosigmoidoscopy
Other: laboratory biomarker analysis
correlative study
Experimental: Arm II (high-dose polyethylene glycol)
Patients receive high-dose polyethylene glycol PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.
Drug: polyethylene glycol
Given PO
Other Names:
  • PEG
  • Poly(oxyethylene)
  • Polyethylene Glycol 400
  • Polyethylene Glycol 8000
  • Polyethylene Oxide
Procedure: colonoscopy
Patients undergo diagnostic procedure
Other Name: colonoscopic studies
Procedure: sigmoidoscopy
Patients undergo diagnostic procedure
Other Name: Proctosigmoidoscopy
Other: laboratory biomarker analysis
correlative study
Placebo Comparator: Arm III (placebo)
Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.
Other: placebo
Given PO
Other Name: PLCB
Procedure: colonoscopy
Patients undergo diagnostic procedure
Other Name: colonoscopic studies
Procedure: sigmoidoscopy
Patients undergo diagnostic procedure
Other Name: Proctosigmoidoscopy
Other: laboratory biomarker analysis
correlative study

Detailed Description:

PRIMARY OBJECTIVE:

I. To evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8g or 17g/day for six months) versus placebo on epidermal growth factor receptor (EGFR) expression.

SECONDARY OBJECTIVES:

I. To determine the effect of PEG 3350 on aberrant crypt foci (ACF) number and to compare 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 messenger ribonucleic acid (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 (PO) once daily (QD).

ARM II: Patients receive high-dose polyethylene glycol PO QD.

ARM III: Patients receive placebo (i.e., maltodextrose powder) PO QD.

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 immunohistochemistry (IHC) and for EGFR and E-cadherin expression by Western blot. Samples are also analyzed for mRNA expression of EGFR and SNAIL by real time-polymerase chain reaction (RT-PCR). Blood samples are collected periodically for RNA isolation.

After completion of study treatment, patients are followed at 30 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 polyethylene glycol (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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (equivalent to Karnofsky >= 70%)
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • International normalized ratio (INR) =< 1.5
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotrnasferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 1.5 X institutional ULN
  • Estimated glomerular filtration rate (eGFR) > 45
  • Blood urea nitrogen (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 nonsteroidal antiinflammatory drug (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 preparation)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00828984

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Investigators
Principal Investigator: Raymond Bergan Northwestern University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00828984     History of Changes
Other Study ID Numbers: NCI-2009-01113, NCI-2009-01113, P30CA060553, NCI 06-8-01, CDR0000632553, N01CN35157, NCI06-8-01, NWU06-8-01, N01CN35157, P30CA060553
Study First Received: January 23, 2009
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenomatous Polyps
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 24, 2014