Clinical trial NCT00099021: Pioglitazone Hydrochloride in Preventing Head and Neck Cancer in Patients With Oral Leukoplakia
Official title: A Phase IIa Cancer Prevention Trial of the PPAR Gamma Agonist Pioglitazone in Oral Leukoplakia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Oral Leukoplakia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-12-09
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Patients' Overall Response
timeFrame: Week 16 (4 weeks post dose)
Secondary outcomes:
measure: Patients' Clinical Response
timeFrame: Week 16 (4 weeks post dose)
measure: Patients' Histological (Tissue) Response
timeFrame: Week 16 (4 weeks post dose)
Other outcomes:
measure: Interleukin 6, 8 and Vascular Endothelial Growth Factors Elaboration in the Oral Cavity and Serum
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Quantitative Oil Red O, AP2 (FABP4) and FABP5 Staining
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Involucrin and Transglutaminase Staining
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Cyclin D1 and p21 Immune Histochemistry
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Cyclooxygenase-2 Staining
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Piogliotazone Gamma Immune Histochemistry
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Ki 67 Labeling Index
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Apotosis (Cell Death)
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
measure: Nf Kappa B p65
timeFrame: Pre (Day 0) and Post (Week 12) Treatment
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
Study officials:
affiliation: University of Minnesota Medical Center-Fairview
name: Frank Ondrey
role: PRINCIPAL_INVESTIGATOR
References: