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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00828984

Enrollment

Registered

2009-01-26

Start date

2009-10-31

Completion date

2014-10-31

Last updated

2017-04-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adenomatous Polyp, Colorectal Carcinoma

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.

Interventions

DRUGmacrogol 3350-based oral osmotic laxative

Given PO

OTHERPlacebo

Given PO

OTHERLaboratory Biomarker Analysis

Correlative studies

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Difference (After Treatment Minus Before Treatment) of EGFR Expression	6 months - baseline	Evaluate the effect of polyethylene glycol (PEG) 3350 (administered at 8g or 17g/day for six months) versus placebo on EGFR expression.

Secondary

Measure	Time frame	Description
Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies	6 months - baseline	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
Change in Ki-67 (Proliferation) Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies	6 months - baseline	To determine the effect of PEG 3350 on mucosal epithelial proliferation (Ki-67)
Change in Mucosal Apoptosis (Cleaved Caspase-3) as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies	6 months - baseline	Change in activated caspase-3 (apoptosis) expression as measured in endoscopically normal (non-ACF) mucosal biopsies
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	—

Countries

United States

Participant flow

Recruitment details

Age 18 and older; Recruitment sites: NorthShore University HealthSystem, University of Chicago, Boston University (no accrual occurred)

Pre-assignment details

History of any size adenoma or colon cancer within the last 6 years;

Participants by arm

Arm	Count
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. macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	28
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. macrogol 3350-based oral osmotic laxative: Given PO Laboratory Biomarker Analysis: Correlative studies	31
Arm C (Placebo) Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies	28
Total	87

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	2	3	0
Overall Study	ConMed	1	1	1
Overall Study	Ineligable	1	2	0
Overall Study	Lost to Follow-up	5	3	1
Overall Study	Medical Contraindication	0	1	0
Overall Study	Noncompliant	1	2	3
Overall Study	Withdrawal by Subject	4	4	4

Baseline characteristics

Characteristic	Arm A (High-dose PEG 3350)	Arm B (Low-dose Polyethylene Glycol)	Arm C (Placebo)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	9 Participants	13 Participants	10 Participants	32 Participants
Age, Categorical Between 18 and 65 years	19 Participants	18 Participants	18 Participants	55 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	2 Participants	0 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants	29 Participants	28 Participants	84 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Black or African American	4 Participants	5 Participants	0 Participants	9 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	24 Participants	26 Participants	26 Participants	76 Participants
Sex: Female, Male Female	14 Participants	17 Participants	12 Participants	43 Participants
Sex: Female, Male Male	14 Participants	14 Participants	16 Participants	44 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	13 / 28	16 / 31	13 / 28
serious Total, serious adverse events	0 / 28	1 / 31	2 / 28

Outcome results

Primary

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.