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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00099021
• Other study ID #: NCI-2009-00862
• Secondary ID: NCI-2009-00862CD
• Status: Completed
• Phase: Phase 2
• Start date: June 2003
• Est. completion date: June 27, 2008

Study information

• Verified date: January 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 27, 2008
• Est. primary completion date: June 27, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Leukoplakia
• Leukoplakia, Oral
• Oral Leukoplakia

Intervention

Drug:
• pioglitazone hydrochloride
Given PO

Locations

Country	Name	City	State
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Interleukin 6, 8 and Vascular Endothelial Growth Factors Elaboration in the Oral Cavity and Serum	Quantitative studies of serum and saliva components for a pre and post treatment possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Quantitative Oil Red O, AP2 (FABP4) and FABP5 Staining	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Involucrin and Transglutaminase Staining	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Cyclin D1 and p21 Immune Histochemistry	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Cyclooxygenase-2 Staining	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Piogliotazone Gamma Immune Histochemistry	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Ki 67 Labeling Index	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Apotosis (Cell Death)	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Other	Nf Kappa B p65	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Primary	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	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)
Secondary	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)