Macrogol 3350-based Oral Osmotic Laxative 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: October 22, 2014
Last verified: September 2014
  Purpose

This randomized phase II trial studies how well macrogol 3350-based oral osmotic laxative (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 macrogol 3350-based oral osmotic laxative may stop cancer from growing in patients who are at risk of colorectal cancer.


Condition Intervention Phase
Adenomatous Polyp
Colorectal Cancer
Drug: macrogol 3350-based oral osmotic laxative
Other: placebo
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: Prevention
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: Baseline to 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 reverse transcriptase (RT)-polymerase chain reaction (PCR).


Secondary Outcome Measures:
  • Change in ACF count as measured in endoscopically normal (non-ACF) mucosal biopsies [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
  • Change in Ki-67 (proliferation) expression as measured in endoscopically normal (non-ACF) mucosal biopsies [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
    Ki-67 will be measured by immunohistochemistry (IHC).

  • Change in activated caspase-3 (apoptosis) expression as measured in endoscopically normal (non-ACF) mucosal biopsies [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
    Activated caspase-3 will be measured by IHC.

  • Change in SNAIL expression as measured in endoscopically normal (non-ACF) mucosal biopsies [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
    SNAIL will be measured by IHC. mRNA expression of SNAIL will be measured by RT-PCR.

  • Change in E-cadherin expression as measured in endoscopically normal (non-ACF) mucosal biopsies [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
    E-cadherin will be measured by immunoblot.


Estimated Enrollment: 140
Study Start Date: October 2009
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (high-dose PEG 3350)
Patients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.
Drug: macrogol 3350-based oral osmotic laxative
Given PO
Other Name: Colonlytely
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (low-dose polyethylene glycol)
Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.
Drug: macrogol 3350-based oral osmotic laxative
Given PO
Other Name: Colonlytely
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm C (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
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVE:

I. To evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8 g or 17 g/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 (8 g PEG 3350/day) and higher dose (17 g PEG 3350/day) groups.

II. To determine the effect of PEG 3350 on mucosal epithelial proliferation (marker of proliferation Ki-67 [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 family zinc finger 1 (SNAIL) protein expression.

V. To determine the effect of PEG 3350 on messenger ribonucleic acid (mRNA) expression of SNAIL and EGFR.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: Patients receive high-dose macrogol 3350-based oral osmotic laxative orally (PO) once daily (QD).

ARM B: Patients receive low-dose macrogol 3350-based oral osmotic laxative PO QD.

ARM C: 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.

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 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 aminotransferase (ALT) (serum glutamate 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 anti-inflammatory 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, inflammatory bowel disease [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: October 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenomatous Polyps
Colorectal Neoplasms
Adenoma
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Cathartics
Laxatives
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014