Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia

Inclusion Criteria:

* Males or females with a suspected or histologically confirmed index oral premalignant lesion (excluding carcinoma in situ), 12mm or greater in size that has not been biopsied in the past 6 weeks; each index lesion must be either a:

  * dysplastic measurable leukoplakia or erythroplakia in the oral cavity or accessible oropharynx, or
  * hyperplastic leukoplakia of high-risk sites, lateral and ventral tongue and floor of mouth
* The subject's life expectancy is \> 12 weeks and Karnofsky performance score is 70-100%
* Hemoglobin and hematocrit levels above the lower limit of normal
* White blood cells \>= 3,000/uL
* Platelets \>= 125,000/uL
* Total bilirubin =\< 1.5 x ULN
* AST (SGOT)/ALT (SGPT) =\< 1.5 x ULN
* BUN and serum creatinine =\< 1.5 x ULN
* LDH =\< 1.5 x ULN
* If the subject is female and of childbearing potential (women are considered not of childbearing potential if they are at least two years postmenopausal and/or surgically sterile), she:

  * has been using adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) since her last menses and will use adequate contraception during the study, AND
  * is not lactating, AND
  * has a documented negative serum pregnancy test within 14 days prior to randomization
* The subject has discontinued any other oral cancer chemopreventive therapy at least 12 weeks prior to the Baseline visit and all toxicities have been fully resolved; daily aspirin is permitted
* The subject is willing and able to fully participate for the duration of the study
* If applicable, the subject has been counseled on smoking cessation
* The effects of rosiglitazone (Avandia) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, and because rosiglitazone has been associated with fetal death and growth retardation in rats and rabbits and placental pathology in rats, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and 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 and will be removed from the trial
* Ability to understand and the willingness to sign a written informed consent document
* The subject is of New York Heart Association (NYHA) Class 1 to 4 cardiac status

Exclusion Criteria:

* The subject has active cancer or carcinoma in situ of the head and neck
* The subject has a contraindication to biopsy
* The subject has any history of congestive heart failure, any history of myocardial infarction, angina, or coronary artery disease within the past 6 months, or active cardiac disease
* The subject exhibits clinical evidence of active liver disease, history of chronic liver disease or edema
* The subject currently receives insulin, sulfonylurea or metformin (doses of rosiglitazone greater than 4 mg daily in combination with these therapies are not currently indicated; because this protocol uses the maximum recommended dose of 8 mg daily, subjects on insulin, sulfonylurea or metformin will be ineligible for participation in this trial); the subject is currently receiving thiazolidinediones; the subject is a diabetic not on treatment or hyperglycemic (has a random blood glucose level \> 200 mg/dl); the subject has diabetic macular edema
* The subject is currently receiving medical therapy for dysregulated blood sugar
* The subject has experienced jaundice with Rezulin® (troglitazone)
* The subject has known hypersensitivity to rosiglitazone, Avandia, or any of its components
* The subject has a history of colorectal cancer, familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC)
* The subject has a history of invasive cancer within the past 18 months (excluding non-invasive bladder cancer, non-melanoma skin cancer and in situ cervical cancer); subjects (excluding those with a history of colorectal cancer, FAP or HNPCC) who received curative treatment and have shown no evidence of recurrence for 18 months will be eligible
* The subject has had chemotherapy, immunotherapy, hormonal therapy (other than HRT for menopause), or radiation therapy within 18 months of the Baseline visit
* The subject will need concurrent chemotherapy, radiotherapy, hormonal (other than HRT for menopause), or immunotherapy during the time of study
* The subject has received any investigational medication within 30 days of the Baseline visit or is scheduled to receive an investigational drug during the course of the study
* The subject participated in the study previously and was withdrawn
* The subject is pregnant or nursing
* Subjects who have had the study drug prior to this study
* The subject has uncontrolled intercurrent illness including: ongoing or active infection, HIV, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements