Pioglitazone Hydrochloride in Preventing Head and Neck Cancer in Patients With Oral Leukoplakia

Study Overview
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Brief Summary
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This phase II trial studies how well pioglitazone hydrochloride works in preventing head and neck cancer in patients who have oral leukoplakia. Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of pioglitazone hydrochloride may be effective in preventing head and neck cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine whether pioglitazone (pioglitazone hydrochloride) reverses leukoplakia in patients with hyperplastic or dysplastic oral cavity or oropharyngeal leukoplakia. SECONDARY OBJECTIVES: I. Determine the safety and tolerability of this drug in these patients. OUTLINE: This is an open-label study. Patients receive pioglitazone hydrochloride orally (PO) once daily (QD) for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma. Patients are followed up at 4, 8, 12, and 16 weeks.

Official Title
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A Phase IIa Cancer Prevention Trial of the PPAR Gamma Agonist Pioglitazone in Oral Leukoplakia

Conditions
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Head and Neck Cancer, Oral Leukoplakia

Intervention / Treatment
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* Drug: pioglitazone hydrochloride


Participation Criteria
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Eligibility Criteria
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Criteria: ECOG 0-2 Diagnosis of oral cavity or oropharyngeal leukoplakia meeting 1 of the following criteria: Biopsy-proven hyperplasia in high-risk anatomic areas (e.g., floor of the mouth, mobile tongue, oropharynx, or in any erythroplakia lesion) Mild, moderate, or severe dysplasia at any site of the oral cavity or oropharynx within the lesion Measurable lesion that is clinically characterized by leukoplakia, erythroplakia, or erythroleukoplakia Able to be assessed by bi-directional measurements Life expectancy: More than 3 months Hemoglobin >= lower limit of normal for males and post-menopausal females OR Hemoglobin >= 11 g/dL for premenopausal females WBC > 3,000/mm^3 Hepatic: Bilirubin < 1.5 times upper limit of normal (ULN); AST and ALT < 1.5 times ULN Renal: BUN < 1.5 times ULN; Creatinine < 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No contraindication to thiazolidinediones No allergy to pioglitazone or other thiazolidinediones No serious oral infection No invasive carcinoma within the past 60 months except nonmelanoma skin cancer or carcinoma in situ of the cervix No concurrent malignancy More than 3 months since prior biologic or immunologic therapy No concurrent insulin for diabetes No prior radiotherapy to the oral cavity More than 3 months since prior chemopreventative agents More than 3 months since prior experimental therapy More than 3 months since prior megadose vitamins or alternative therapy No prior thiazolidinediones No prior participation in this study No concurrent pharmacologic treatment for diabetes Concurrent chronic use of non-steroidal anti-inflammatory drugs allowed Platelet count > 125,000/mm^3 Index lesion must be located in an anatomic site accessible by punch biopsy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention (pioglitazone hydrochloride)<br>Patients receive pioglitazone hydrochloride PO QD for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma. | Drug: pioglitazone hydrochloride<br>* Given PO<br>* Other names: pioglitazone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Overall Response | Overall Response= reviewing both the clinical and histological responses and assigning the worst category. Complete Response (CR) = Clinical CR and Histologic CR, or Histologic CR Partial Response (PR) = Clinical CR or PR and Histologic PR or Stable Disease (SD) Stable Disease (SD) = Clinical SD and Histologic PR or SD Progressive Disease (PD) = Clinical PD and/or Histologic PD | Week 16 (4 weeks post dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' Clinical Response | Determined by measurement of lesions- Complete Response (CR)= disappearance of all lesions, Partial Response (PR)= >or= 50% decrease in sum of lesions, Stable Disease (SD) = does not meet CR,PR or Progressive Disease (PD), and PD= >or= 25% increase in sum of lesions | Week 16 (4 weeks post dose) | 
| Patients' Histological (Tissue) Response | Determined by biopsy results before and 4 weeks after treatment: Complete Response (CR) =complete reversal of dysplasia or hyperplasia, Partial Response (PR) = >or=50% decrease in sum of lesions, no increase in 1 or more lesions and no new lesion occurs, Stable Disease (SD0 = not CR, PR or Progressive Disease (PD), PD = >or= 25% increase in sum of lesions or new lesion or progression to invasive carcinoma. | Week 16 (4 weeks post dose) |