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

Colorectal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00828984
• Other study ID #: NCI-2009-01113
• Secondary ID: NCI-2009-01113NC
• Status: Completed
• Phase: Phase 2
• First received: January 23, 2009
• Last updated: March 6, 2015
• Start date: October 2009
• Est. completion date: October 2014

Study information

• Verified date: February 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Adenomatous Polyp
• Adenomatous Polyps
• Colorectal Carcinoma

Intervention

Drug:
• macrogol 3350-based oral osmotic laxative
Given PO

Other:
• Placebo
Given PO
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference A-B (After treatment minus Before treatment) of EGFR expression	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).	Baseline to up to 6 months	No
Secondary	Change in ACF count as measured in endoscopically normal (non-ACF) mucosal biopsies		Baseline to up to 6 months	No
Secondary	Change in Ki-67 (proliferation) expression as measured in endoscopically normal (non-ACF) mucosal biopsies	Ki-67 will be measured by immunohistochemistry (IHC).	Baseline to up to 6 months	No
Secondary	Change in activated caspase-3 (apoptosis) expression as measured in endoscopically normal (non-ACF) mucosal biopsies	Activated caspase-3 will be measured by IHC.	Baseline to up to 6 months	No
Secondary	Change in SNAIL expression as measured in endoscopically normal (non-ACF) mucosal biopsies	SNAIL will be measured by IHC. mRNA expression of SNAIL will be measured by RT-PCR.	Baseline to up to 6 months	No
Secondary	Change in E-cadherin expression as measured in endoscopically normal (non-ACF) mucosal biopsies	E-cadherin will be measured by immunoblot.	Baseline to up to 6 months	No