Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus
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ClinicalTrials.gov Identifier: NCT01447927 |
Recruitment Status
:
Completed
First Posted
: October 6, 2011
Results First Posted
: July 21, 2014
Last Update Posted
: July 21, 2014
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Tracking Information | ||||
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First Submitted Date ICMJE | October 5, 2011 | |||
First Posted Date ICMJE | October 6, 2011 | |||
Results First Submitted Date | April 2, 2014 | |||
Results First Posted Date | July 21, 2014 | |||
Last Update Posted Date | July 21, 2014 | |||
Study Start Date ICMJE | June 2012 | |||
Actual Primary Completion Date | May 2013 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Percent Change in Median pS6K1 Immunostaining Among Participants With Barrett Esophagus [ Time Frame: Baseline to 3 months ] The percent change in pS6K1 was calculated as month 3 pS6k1 values minus baseline pS6k1 values, then divide by baseline pS6k1 values and multiply by 100.
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Original Primary Outcome Measures ICMJE |
Percent change in mean pS6K1 values using the Wilcoxon Rank-Sum test | |||
Change History | Complete list of historical versions of study NCT01447927 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
Overall Adverse Event Rates [ Time Frame: Up to 30 days ] Number of patients that experienced adverse events (grade 1 or above) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v. 4.0. The data reported in the table include only the commonly occurring adverse events (3 or more events). |
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Original Secondary Outcome Measures ICMJE |
Adverse events as assessed by NCI CTC v. 4.0 | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus | |||
Official Title ICMJE | Randomized Double Blind Placebo Controlled Trial of Barrett's Esophagus Chemoprevention With Metformin | |||
Brief Summary | This randomized phase II trial studies how well metformin hydrochloride works in preventing esophageal cancer in patients with Barrett esophagus. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of metformin hydrochloride may keep esophageal cancer from forming. | |||
Detailed Description | PRIMARY OBJECTIVES: I. To compare the percent change in the mean pS6K1 immunostaining from baseline in mucosal Barrett esophagus (BE) biopsies among patients assigned to 2,000 mg metformin hydrochloride once daily (QD) versus placebo as determined from Barrett mucosal biopsy samples obtained pre- and post-intervention. SECONDARY OBJECTIVES: I. To evaluate adverse events associated with the two intervention arms. TERTIARY OBJECTIVES: I. To assess the effects of metformin hydrochloride 2,000 mg QD versus placebo on the changes in pS6K1 using traditional IHC categories. II. To assess the effects of metformin hydrochloride 2,000 mg QD versus placebo on absolute change in pS6K1. III. To assess changes in serum markers (metformin hydrochloride, fasting insulin, HOMA-IR, IGF-1, IGF-2, IGFBP-1, IGFBP-3, fasting leptin, and fasting adiponectin) as determined from serum samples obtained pre- and post-intervention. IV. To assess changes in proliferation (Ki-67) and apoptosis (cleaved caspase 3) as determined from Barrett mucosal biopsy samples obtained pre- and post-intervention. V. To assess changes in molecular mediators of the insulin pathway (p-IRS-1, p-AKT^Serine 473) as determined from Barrett mucosal biopsy samples obtained pre- and post-intervention. VI. To assess changes in relative activity of AMPK (phosphorylated AMPK/total AMPK ratio) and molecular mediators of AMP kinase (p-mTOR, pS6K1^Serine 235) as determined from Barrett mucosal biopsy samples obtained pre- and post-intervention. VII. To assess changes in Programmed Cell Death 4 expression and miR-21 as determined from Barrett mucosal biopsy samples pre- and post-intervention. VIII. To establish a biospecimen repository archive for future correlative studies. OUTLINE: This is a multicenter study. Patients are stratified according to nonsteroidal anti-inflammatory drugs use (regular vs no regular), body mass index (≥ 30 kg/m² vs < 30 kg/m²), gender (male vs female), and length of Barrett (2.00 to 4.99 cm vs ≥ 5.00 cm). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD) on week 1, and twice daily (BID) on weeks 2-12 (every morning [QAM] and every evening [QPM] on week 3) in the absence of unacceptable toxicity or disease progression. Arm II: Patients receive extended-release placebo PO QD on week 1 and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression. Blood, tissue, and mucosal tissue samples are collected at baseline and after completion of study treatment for pS6K1 analysis and other serum, mucosal, and molecular markers studies by IHC, ELISA, western blotting, and high-performance liquid chromatography (HPLC) methods. After completion of study treatment, patients are followed up for 30 days. |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Prevention |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms |
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Publications * | Chak A, Buttar NS, Foster NR, Seisler DK, Marcon NE, Schoen R, Cruz-Correa MR, Falk GW, Sharma P, Hur C, Katzka DA, Rodriguez LM, Richmond E, Sharma AN, Smyrk TC, Mandrekar SJ, Limburg PJ; Cancer Prevention Network. Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett's esophagus. Clin Gastroenterol Hepatol. 2015 Apr;13(4):665-72.e1-4. doi: 10.1016/j.cgh.2014.08.040. Epub 2014 Sep 15. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
93 | |||
Original Estimated Enrollment ICMJE |
86 | |||
Actual Study Completion Date | September 2013 | |||
Actual Primary Completion Date | May 2013 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Senior) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Canada, Puerto Rico, United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01447927 | |||
Other Study ID Numbers ICMJE | NCI-2011-03451 MAY10-15-03 MAYO-MAY10-15-03 CDR0000698069 |
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Has Data Monitoring Committee | Not Provided | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Responsible Party | National Cancer Institute (NCI) | |||
Study Sponsor ICMJE | National Cancer Institute (NCI) | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | |||
Verification Date | June 2014 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |