Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01447927
First received: October 5, 2011
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Barrett Esophagus
Esophageal Cancer
Drug: metformin hydrochloride
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Randomized Double Blind Placebo Controlled Trial of Barrett's Esophagus Chemoprevention With Metformin

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percent Change in Median pS6K1 Immunostaining Among Participants With Barrett Esophagus [ Time Frame: Baseline to 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Adverse Event Rates [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]

    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).



Enrollment: 93
Study Start Date: June 2012
Study Completion Date: September 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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
Given PO QD and BID
Other Name: Glucophage
Placebo Comparator: Arm II
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
Given PO QD and BID
Other Name: PLCB

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • No contraindication to esophagogastroduodenoscopy (EGD)
  • Willingness, for both men and women, to use adequate contraception (hormonal or barrier method of birth control; surgical intervention; abstinence) prior to study entry and for the duration of study participation
  • A negative (serum or urine) pregnancy test done =< 7 days prior to Pre-Registration, for women of childbearing potential only
  • No pregnant or nursing women
  • No participants with diabetes mellitus
  • No history of vitamin B12 deficiency or megaloblastic anemia
  • No history of lactic acidosis
  • No diseases associated with weight loss: anorexia, bulimia, or nausea
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin
  • No participants with HIV, cirrhosis of any cause, NASH (non-alcoholic steatohepatitis), or hepatitis (auto-immune or infectious)

    • For participants diagnosed with any other hepatic impairment, consult with protocol principal investigator (PI)
  • No metabolic acidosis, acute or chronic, including ketoacidosis
  • No 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; this includes significant medical conditions including renal failure, hepatic failure, sepsis, and hypoxia
  • No genetics disorders such as family history of hereditary gastrointestinal polyp disorder (e.g., familial adenomatous polyposis [FAP], hereditary non-polyposis colorectal cancer [HNPCC], Peutz-Jegher disease)
  • No chronic alcohol use or a history of alcohol abuse (defined as ingestion of >= 3 drinks per day)
  • No kidney disease or renal insufficiency (defined as serum creatinine outside the normal institutional limits)
  • Currently on a proton pump inhibitor (PPI) >= 4 weeks (any PPI taken at least once daily is acceptable)
  • No medication(s) for weight loss ≤ 2 months prior to Pre-Registration
  • No treatment with medications that may increase metformin hydrochloride levels: cationic drugs, e.g., digoxin, amiloride, procainamide, ranitidine, trimethoprim, quinidine, quinine, vancomycin, triamterene, and morphine
  • No treatment with other oral hypoglycemic agents
  • No participant use of metformin, cimetidine (Tagamet), furosemide (Lasix), or nifedipine (Cardizem), or any other drug contraindicated for use with metformin
  • No receipt of any other investigational agents =< 3 months prior to Pre-Registration, except innocuous agents with no known interaction with the study agent (e.g., standard dose multivitamins or topical agents for limited skin conditions), at the discretion of the Protocol Lead Investigator at each Participating Site
  • No participants who have undergone ablation or other local therapies (e.g., percutaneous dilatational tracheostomy [PDT], cryotherapy, radiofrequency, argon plasma coagulation [APC], or multipolar electrocoagulation [MPEC])

    • Patients treated with endoscopic mucosal resection [EMR] allowed
  • No participants anticipating elective surgery during the study period
  • No participants planning to undergo elective radiologic studies involving intravascular administration of iodinated contrast materials
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01447927

Locations
United States, Illinois
Hines Veterans Administration Hospital
Hines, Illinois, United States, 60141
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pittsburgh Medical Center - Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15232
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5S 1A1
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Investigators
Principal Investigator: Amitabh Chak Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01447927     History of Changes
Other Study ID Numbers: NCI-2011-03451, MAY10-15-03, MAYO-MAY10-15-03, CDR0000698069
Study First Received: October 5, 2011
Results First Received: April 2, 2014
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Esophageal Neoplasms
Barrett Esophagus
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Abnormalities
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014