Clinical Trial: Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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:

Current Secondary Outcome:

  • 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:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 24, 2006
Date Started: June 2006
Date Completion:
Last Updated: February 12, 2013
Last Verified: January 2013