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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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 stud
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Difference (After Treatment Minus Before Treatment) of EGFR Expression [ Time Frame: 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.


Original Primary Outcome: Treatment-related changes in the number of aberrant crypt foci (ACF)

Current Secondary Outcome:

  • Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 6 months - baseline ]
  • Change in E-cadherin Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies [ Time Frame: 6 months - baseline ]


Original Secondary Outcome:

  • Changes in Ki-67 (proliferation), activated caspase-3 (apoptosis), EGFR, SNAIL and E-cadherin expression as measured in endoscopically normal (non-ACF) mucosal biopsies by IHC or Western blot
  • mRNA expression of EGFR and SNAIL as measured by RT-PCR


Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 23, 2009
Date Started: October 2009
Date Completion:
Last Updated: March 22, 2017
Last Verified: March 2017