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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00099021
First received: December 8, 2004
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Oral Leukoplakia
Drug: pioglitazone hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase IIa Cancer Prevention Trial of the PPAR Gamma Agonist Pioglitazone in Oral Leukoplakia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Patients' Overall Response [ Time Frame: Week 16 (4 weeks post dose) ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • Patients' Clinical Response [ Time Frame: Week 16 (4 weeks post dose) ] [ Designated as safety issue: No ]
    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

  • Patients' Histological (Tissue) Response [ Time Frame: Week 16 (4 weeks post dose) ] [ Designated as safety issue: No ]
    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.

  • Nf Kappa B p65 [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Ki 67 Labeling Index [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Apotosis (Cell Death) [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Pigliotazone Gamma Immune Histochemistry [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Cyclooxygenase-2 Staining [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Cyclin D1 and p21 Immune Histochemistry [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Involucrin and Transglutaminase Staining [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Quantitative Oil Red O, AP2 (FABP4) and FABP5 Staining [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Immune histochemistry / tissue staining for a possible biomarker.

  • Interleukin 6, 8 and Vascular Endothelial Growth Factors Elaboration in the Oral Cavity and Serum [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ] [ Designated as safety issue: No ]
    Quantitative studies of serum and saliva components for a pre and post treatment possible biomarker.


Enrollment: 33
Study Start Date: June 2003
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00099021

Locations
United States, Minnesota
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Investigators
Principal Investigator: Frank Ondrey University of Minnesota Medical Center-Fairview
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00099021     History of Changes
Other Study ID Numbers: NCI-2009-00862, 0109 M 07254, CDR0000393562, 2001LS068, N01CN15000
Study First Received: December 8, 2004
Results First Received: October 13, 2009
Last Updated: May 15, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Head and Neck Neoplasms
Leukoplakia
Leukoplakia, Oral
Neoplasms by Site
Neoplasms
Precancerous Conditions
Pathological Conditions, Anatomical
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014