Adenomatous PolypPhase 2NCT00828984
Macrogol 3350-based Oral Osmotic Laxative in Preventing Cancer in Patients at Risk of Colorectal Cancer
A Phase 2 study testing macrogol 3350-based oral osmotic laxative and Laboratory Biomarker Analysis in people with Adenomatous Polyp and Colorectal Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenomatous Polyp, Colorectal Carcinoma
- What is being tested?
- macrogol 3350-based oral osmotic laxative and Laboratory Biomarker Analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2009to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Boston Medical Center
Boston, Massachusetts, 02118
University of Chicago
Chicago, Illinois, 60637
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
About this study
Official title: Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Being tested
- macrogol 3350-based oral osmotic laxative, Placebo, Laboratory Biomarker Analysis
- Medical subject headings
- Adenomatous Polyps, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
macrogol 3350-based oral osmotic laxativeDrug
Also called Colonlytely
Given PO
PlaceboOther
Also called PLCB
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Other: Placebo; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months - baseline
Secondary outcomes (5)
Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
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
Measured: 6 months - baseline
Change in Ki-67 (Proliferation) Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
To determine the effect of PEG 3350 on mucosal epithelial proliferation (Ki-67)
Measured: 6 months - baseline
Change in Mucosal Apoptosis (Cleaved Caspase-3) as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Change in activated caspase-3 (apoptosis) expression as measured in endoscopically normal (non-ACF) mucosal biopsies
Measured: 6 months - baseline
Change in SNAIL Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Measured: 6 months - baseline
Change in E-cadherin Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Measured: 6 months - baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2009 (estimated)
- Study startOct 2009
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenomatous PolypStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Seema Khan, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00828984
- Sponsor's protocol ID
- NCI-2009-01113
- Other IDs
- NCI-2009-01113, NCI 06-8-01, CDR0000632553, N01CN35157, NCI06-8-01, NWU06-8-01, P30CA060553
- Status last verified
- Mar 2017
- First submitted
- 23 Jan 2009
- Last updated
- 18 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 29617381
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk
- ClinicalTrials.gov ID
- NCT00828984
- Acronym / sponsor ID
- NCI-2009-01113
- Conditions
- Adenomatous Polyp, Colorectal Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2009
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 26 Jan 2009 (estimated)
- Results
- Posted 19 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A (high-dose PEG 3350) | Experimental | Drug: macrogol 3350-based oral osmotic laxative, Other: Laboratory Biomarker AnalysisPatients receive high-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. |
| Arm B (low-dose polyethylene glycol) | Experimental | Drug: macrogol 3350-based oral osmotic laxative, Other: Laboratory Biomarker AnalysisPatients receive low-dose macrogol 3350-based oral osmotic laxative PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. |
| Arm C (placebo) | Placebo comparator | Other: Placebo, Other: Laboratory Biomarker AnalysisPatients receive placebo PO QD. Treatment continues for up to 6 months in the absence of unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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%)
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| macrogol 3350-based oral osmotic laxativeAlso: ColonlytelyGiven PO | Drug | Arm A (high-dose PEG 3350), Arm B (low-dose polyethylene glycol) |
| PlaceboAlso: PLCBGiven PO | Other | Arm C (placebo) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm A (high-dose PEG 3350), Arm B (low-dose polyethylene glycol), Arm C (placebo) |
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.
5 secondary outcomes
Change in ACF Count as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Time frame: 6 months - baseline
Change in Ki-67 (Proliferation) Expression as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Time frame: 6 months - baseline
Change in Mucosal Apoptosis (Cleaved Caspase-3) as Measured in Endoscopically Normal (Non-ACF) Mucosal Biopsies
Time frame: 6 months - baseline
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29617381Wali 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seema Khan principal investigator
Northwestern University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing macrogol 3350-based oral osmotic laxative and Laboratory Biomarker Analysis in people with Adenomatous Polyp and Colorectal Carcinoma, run by National Cancer Institute (NCI) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference (After Treatment Minus Before Treatment) of EGFR Expression (time frame: 6 months - baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00828984, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2017.