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

NCT ID: NCT00828984

Last Updated: 2017-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-10-31

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.

Detailed Description

PRIMARY OBJECTIVES:

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.

Conditions

Adenomatous Polyp; Colorectal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

macrogol 3350-based oral osmotic laxative

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: EXPERIMENTAL

macrogol 3350-based oral osmotic laxative

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Arm C (placebo)

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

macrogol 3350-based oral osmotic laxative

Given PO

Intervention Type: DRUG

Placebo

Given PO

Intervention Type: OTHER

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Colonlytely; PLCB

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Seema Khan

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

University of Chicago

Chicago, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Boston Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29617381 (View on PubMed)

Other Identifiers

NCI-2009-01113

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI 06-8-01

Identifier Type: -

Identifier Source: secondary_id

CDR0000632553

Identifier Type: -

Identifier Source: secondary_id

N01CN35157

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI06-8-01

Identifier Type: OTHER

Identifier Source: secondary_id

NWU06-8-01

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-01113

Identifier Type: -

Identifier Source: org_study_id