Macrogol 3350-based Oral Osmotic Laxative in Preventing Cancer in Patients at Risk of Colorectal Cancer

NCT00828984 | Completed Phase 2 Results DMC

• 7 other identifiers: NCI-2009-01113NCI 06-8-01CDR0000632553N01CN35157NCI06-8-01NWU06-8-01P30CA060553
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Adenomatous Polyp; Colorectal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Difference (After Treatment Minus Before Treatment) of EGFR Expression

  Evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8g or 17g/day for six months) versus placebo on EGFR expression.

  6 months - baseline

Secondary Outcomes (5)

• Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies

  6 months - baseline

• Change in Ki-67 (Proliferation) Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies

  6 months - baseline

• Change in Mucosal Apoptosis (Cleaved Caspase-3) as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies

  6 months - baseline

• Change in SNAIL Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies

  6 months - baseline

• Change in E-cadherin Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies

  6 months - baseline

Study Arms (3)

Arm A (high-dose PEG 3350)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis

Arm B (low-dose polyethylene glycol)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis

Arm C (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity.

Other: Placebo; Other: Laboratory Biomarker Analysis

Interventions

macrogol 3350-based oral osmotic laxative DRUG

Given PO

Also known as: Colonlytely

Arm A (high-dose PEG 3350); Arm B (low-dose polyethylene glycol)

Placebo OTHER

Given PO

Also known as: PLCB

Arm C (placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (high-dose PEG 3350); Arm B (low-dose polyethylene glycol); Arm C (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (1)

• Wali RK, Bianchi L, Kupfer S, De La Cruz M, Jovanovic B, Weber C, Goldberg MJ, Rodriguez LM, Bergan R, Rubin D, Tull MB, Richmond E, Parker B, Khan S, Roy HK. Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial. PLoS One. 2018 Apr 4;13(4):e0193544. doi: 10.1371/journal.pone.0193544. eCollection 2018.

  PMID: 29617381 DERIVED

MeSH Terms

Conditions

Adenomatous Polyps; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Dr. Seema Khan
• Organization: Northwestern University

s-khan2@northwestern.edu

312-503-4236

Study Officials

• Seema Khan

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2009
• First Posted: January 26, 2009
• Study Start: October 1, 2009
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 18, 2017
• Results First Posted: January 19, 2017

Record last verified: 2017-03

Locations

US (3)