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Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00369174
Recruitment Status : Completed
First Posted : August 29, 2006
Last Update Posted : February 13, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE August 24, 2006
First Posted Date  ICMJE August 29, 2006
Last Update Posted Date February 13, 2013
Study Start Date  ICMJE June 2006
Actual Primary Completion Date August 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2012)
Proportion of subjects who show complete or partial response in either clinical or histological outcomes [ Time Frame: 12 weeks ]
Estimated together with 95% confidence interval. The confidence interval will be constructed using exact binomial confidence intervals (rather than the normal approximation).
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00369174 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2012)
  • Tissue expressions of COX-2, cyclin D1, Ki-67, p21/waf1, PPAR gamma, K1 cytokeratin, involucrin, and transglutaminase, and tissues levels of apoptosis (assessed using TUNEL) [ Time Frame: 12 weeks ]
    Summarized at each time point using summary statistics such as the mean, median, and range. The changes in levels of these biomarkers will also be explored with similar summary statistics and with graphical methods as well.
  • Tissue DNA ploidy [ Time Frame: 12 weeks ]
  • Smoking and alcohol use [ Time Frame: Up to 12 weeks ]
    Assessed descriptively. Fisher's exact test may be used to assess whether there is a significant association between smoking status and efficacy of rosiglitazone.
  • Adverse events defined as any untoward medical occurrence in a study participant, graded using the NCI CTCAE version 3.0 [ Time Frame: Up to 12 weeks ]
    Descriptively summarized in tabular form.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia
Official Title  ICMJE Phase IIA Trial of Rosiglitazone (Avandia) for Oral Leukoplakia
Brief Summary This phase II trial is studying how well rosiglitazone works in preventing oral cancer in patients with oral leukoplakia. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of rosiglitazone may keep cancer from forming in patients with oral leukoplakia
Detailed Description


I. To determine the rate of clinical response of oral premalignant lesions (OPL) to 12 weeks of therapy with rosiglitazone (Avandia), 8 mg daily, defined as greater than or equal to 50% reduction in the measured product of perpendicular dimension of the target lesion, or improvement in the degree of dysplasia.


I. To determine the rate and degree of change of putative biomarkers of rosiglitazone efficacy including:

COX-2, cyclin D1, Ki-67, p21/waf1, PPAR gamma, K1 cytokeratin, involucrin, transglutaminase expressions, and TUNEL.

II. To estimate the correlation between DNA ploidy measurements in OPL with clinical response and or response of biomarkers to rosiglitazone therapy, and to estimate the efficacy of rosiglitazone therapy to normalize aberrant DNA ploidy in OPL.

III. To thoroughly assess smoking patterns among trial participants and to examine the relationship of smoking to treatment response.

IV. To assess the safety of this agent in short-term use in this population.

OUTLINE: This is a multicenter, open-label, nonrandomized study.

Patients receive oral rosiglitazone once daily. Treatment continues for 12 weeks in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed at 1 week.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Oral Leukoplakia
Intervention  ICMJE
  • Drug: rosiglitazone maleate
    Given orally
    Other Names:
    • Avandia
    • BRL49653
    • ROS
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (rosiglitazone maleate)
Patients receive oral rosiglitazone once daily. Treatment continues for 12 weeks in the absence of unacceptable toxicity.
  • Drug: rosiglitazone maleate
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 19, 2012)
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date August 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Norway
Administrative Information
NCT Number  ICMJE NCT00369174
Other Study ID Numbers  ICMJE NCI-2012-02968
N01CN35159 ( U.S. NIH Grant/Contract )
P30CA008748 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jay Boyle Memorial Sloan Kettering Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP