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Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia

Primary Purpose

Oral Leukoplakia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rosiglitazone maleate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Oral Leukoplakia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (rosiglitazone maleate)

Arm Description

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

Outcomes

Primary Outcome Measures

Proportion of subjects who show complete or partial response in either clinical or histological outcomes
Estimated together with 95% confidence interval. The confidence interval will be constructed using exact binomial confidence intervals (rather than the normal approximation).

Secondary Outcome Measures

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)
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
Smoking and alcohol use
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
Descriptively summarized in tabular form.

Full Information

First Posted
August 24, 2006
Last Updated
February 12, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00369174
Brief Title
Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia
Official Title
Phase IIA Trial of Rosiglitazone (Avandia) for Oral Leukoplakia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Leukoplakia

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (rosiglitazone maleate)
Arm Type
Experimental
Arm Description
Patients receive oral rosiglitazone once daily. Treatment continues for 12 weeks in the absence of unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
rosiglitazone maleate
Other Intervention Name(s)
Avandia, BRL49653, ROS
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Proportion of subjects who show complete or partial response in either clinical or histological outcomes
Description
Estimated together with 95% confidence interval. The confidence interval will be constructed using exact binomial confidence intervals (rather than the normal approximation).
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
12 weeks
Title
Tissue DNA ploidy
Time Frame
12 weeks
Title
Smoking and alcohol use
Description
Assessed descriptively. Fisher's exact test may be used to assess whether there is a significant association between smoking status and efficacy of rosiglitazone.
Time Frame
Up to 12 weeks
Title
Adverse events defined as any untoward medical occurrence in a study participant, graded using the NCI CTCAE version 3.0
Description
Descriptively summarized in tabular form.
Time Frame
Up to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jay Boyle
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

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Rosiglitazone Maleate in Treating Patients With Oral Leukoplakia

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