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

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Oral Leukoplakia
• Intervention / Treatment: Drug: pioglitazone hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center-Fairview

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prevention (pioglitazone hydrochloride); 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; Given PO; Other Names: Actos; pioglitazone

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Involucrin and Transglutaminase Staining	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Cyclin D1 and p21 Immune Histochemistry	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Cyclooxygenase-2 Staining	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Piogliotazone Gamma Immune Histochemistry	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Ki 67 Labeling Index	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Apotosis (Cell Death)	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment
Nf Kappa B p65	Immune histochemistry / tissue staining for a possible biomarker.	Pre (Day 0) and Post (Week 12) Treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Frank Ondrey, University of Minnesota Medical Center-Fairview

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): June 27, 2008
• Study Completion (Actual): June 27, 2008

Study Registration Dates

• First Submitted: December 8, 2004
• First Submitted That Met QC Criteria: December 8, 2004
• First Posted (Estimate): December 9, 2004

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Stomatognathic Diseases; Mouth Diseases; Pathological Conditions, Anatomical; Precancerous Conditions; Mouth Neoplasms; Head and Neck Neoplasms; Leukoplakia; Leukoplakia, Oral; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: NCI-2009-00862 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000393562; 2001LS068; 0109 M 07254 (Other Identifier: University of Minnesota Medical Center-Fairview); N01-CN-15000 (Other Identifier: DCP); N01CN15000 (Other Identifier: US NIH Grant/Contract Award Number)