Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus

NCT01447927 | Completed Phase 2 Results

• 4 other identifiers: NCI-2011-03451MAY10-15-03MAYO-MAY10-15-03CDR0000698069
• Study Type: interventional
• Target: 93
• Locations: 3 countries
• Sites: 7

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.

Conditions

Barrett Esophagus; Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Percent Change in Median pS6K1 Immunostaining Among Participants With Barrett Esophagus

  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.

  Baseline to 3 months

Secondary Outcomes (1)

• Overall Adverse Event Rates

  Up to 30 days

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.

Drug: metformin hydrochloride

Arm II

PLACEBO COMPARATOR

Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.

Other: placebo

Interventions

metformin hydrochloride DRUG

Given PO QD and BID

Also known as: Glucophage

Arm I

placebo OTHER

Given PO QD and BID

Also known as: PLCB

Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of Barrett esophagus, with no dysplasia, indeterminate for dysplasia, or low-grade dysplasia as defined by the presence of specialized columnar epithelium on histology and \>= 2 cm of involvement on endoscopy
• Adequate Barrett mucosa, which is defined as \>= 1 out of 4 research samples (i.e., \>= 25%) with \>= 50% intestinal metaplasia in biopsies required to satisfy the endpoints of the study
• No history of esophageal carcinoma or other cancer(s) (except for non-melanoma skin cancers)
• No erosive esophagitis or ulcerative esophagitis, unless treatment with a proton pump inhibitor (PPI) results in healed erosions or ulcers prior to entry endoscopy
• No history of high-grade dysplasia or cancer (confirmed locally by esophagogastroduodenoscopy \[EGD\] and Pathology reports)
• No ulcer, plaque, nodule, stricture, or other luminal irregularity within the Barrett segment, unless clinical biopsy produces no evidence of high-grade dysplasia or cancer
• ECOG performance status =\< 1
• Hemoglobin \>= 10 g/dL
• Leukocytes \>= 3,000/mL (\>= 2,500/mL for African-American participants)
• Absolute neutrophil count \>= 1,500/mL (\>= 1,000/mL for African-American participants)
• Platelets \>= 100,000/mL
• Total bilirubin =\< institutional upper limit of normal (ULN)
• AST (SGOT) and ALT (SGPT) =\< 1.5 times institutional ULN
• Creatinine =\< institutional ULN
• Willingness to provide tissue samples for research purposes

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Hines Veterans Administration Hospital

Hines, Illinois, 60141, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

University of Pittsburgh Medical Center - Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Toronto

Toronto, Ontario, M5S 1A1, Canada

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 25218668 DERIVED

MeSH Terms

Conditions

Barrett Esophagus; Esophageal Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Amitabh Chak
• Organization: University Hospitals of Cleveland, Case Medical Center

Amitabh.chak@case.edu

216-844-5385

Study Officials

• Amitabh Chak

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 6, 2011
• Study Start: June 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 21, 2014
• Results First Posted: July 21, 2014

Record last verified: 2014-06

Locations

CA (1); US (5); PR (1)