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

NCT00099021 | Completed Phase 2 Results

• 6 other identifiers: NCI-2009-00862CDR00003935622001LS0680109 M 07254N01-CN-15000N01CN15000
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Head and Neck Cancer; Oral Leukoplakia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Patients' Clinical Response

  Week 16 (4 weeks post dose)

• Patients' Histological (Tissue) Response

  Week 16 (4 weeks post dose)

Other Outcomes (9)

• Interleukin 6, 8 and Vascular Endothelial Growth Factors Elaboration in the Oral Cavity and Serum

  Pre (Day 0) and Post (Week 12) Treatment

• Quantitative Oil Red O, AP2 (FABP4) and FABP5 Staining

  Pre (Day 0) and Post (Week 12) Treatment

• Involucrin and Transglutaminase Staining

  Pre (Day 0) and Post (Week 12) Treatment

Study Arms (1)

Prevention (pioglitazone hydrochloride)

EXPERIMENTAL

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

Interventions

pioglitazone hydrochloride DRUG

Given PO

Also known as: Actos, pioglitazone

Prevention (pioglitazone hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• Gates JC, Abouyared M, Shnayder Y, Farwell DG, Day A, Alawi F, Moore M, Holcomb AJ, Birkeland A, Epstein J. Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service. Head Neck. 2025 Feb;47(2):733-741. doi: 10.1002/hed.28013. Epub 2024 Nov 25.

  PMID: 39584361 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Leukoplakia, Oral

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Neoplasms; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study was closed prior to full accrual because results were very good and funding was discontinued (R-01 application was filed.) Immunohistochemistry (Outcomes #4 through #12) were not done due to laboratory limitations of time.

Results Point of Contact

• Title: Frank G. Ondrey, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

ondre002@umn.edu

612-625-3200

Study Officials

• Frank Ondrey

  University of Minnesota Medical Center-Fairview

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2004
• First Posted: December 9, 2004
• Study Start: June 1, 2003
• Primary Completion: June 27, 2008
• Study Completion: June 27, 2008
• Last Updated: February 11, 2022
• Results First Posted: November 25, 2009

Record last verified: 2022-01

Locations

US (1)