Pioglitazone in Preventing Head and Neck Cancer in Patients With Oral Leukoplakia - Full Text View

Sponsor:	Masonic Cancer Center, University of Minnesota
Information provided by:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00099021

Purpose

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of pioglitazone may be effective in preventing head and neck cancer.

PURPOSE: This phase II trial is studying the effectiveness of pioglitazone in preventing head and neck cancer in patients who have oral leukoplakia.

Condition	Intervention	Phase
Head and Neck Cancer Precancerous Condition Neoplasms Oral Leukoplakia	Drug: pioglitazone hydrochloride	Phase II

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

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:	21
Study Start Date:	June 2003
Study Completion Date:	September 2008
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pioglitazone Patients Patients treated with Pioglitazone.	Drug: pioglitazone hydrochloride oral pill, 45 mg, every morning, by mouth Other Names: Pioglitazone Actos(TM)

Detailed Description:

OBJECTIVES:

Primary

Determine whether pioglitazone reverses leukoplakia in patients with hyperplastic or dysplastic oral cavity or oropharyngeal leukoplakia.

Secondary

Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is an open-label study.

Patients receive oral pioglitazone once daily for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma.

Patients are followed at 4, 8, 12, and 16 weeks.

Response Definitions-

Clinical Response:
- Complete Clinical Response (CCR): Disappearance of all evidence of all measurable lesions for at least 4 weeks.
- Partial Clinical Response (PCR): 50% or greater decrease in the sum of products of diameters of all measurable lesions persisting for 4 weeks. No lesion may increase in size and no new lesion may appear.
- Stable Clinical Disease (SCD): Changes in size that do not meet CCR, CPR or Progressive Clinical Disease(PCD).
- Progressive Clinical Disease (PCD): Any increase greater than or equal to 25% in the sum of the products of the diameters of the index lesion, or the appearance of an unequivocal new lesion or progression to invasive carcinoma.
Histologic Response (at Week 12):
- Complete Histologic Response (CHR): Complete reversal of dysplasia or hyperplasia to normal epithelium in index lesion and all other premalignant lesions.
- Partial Histologic Response (PHR): Improvement of the degree of dysplasia or hyperplasia in any biopsied premalignant lesion from advanced to early or from early to normal epithelium with no change in any other biopsied lesions.
- Stable Histologic Disease (SHD): No change in the degree of dysplasia in the selected lesion.
- Progressive Histologic Disease (PHD): Any increase in the severity of grade of histology or progression to a carcinoma in the premalignant index lesion.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Objective evidence of oral leukoplakia (may be clinically characterized by leukoplakia, erythroplakia, erythro/leukoplakia; located in oral cavity of oropharynx.
Biopsy-proven hyperplasia in high-risk anatomic areas (floor of mouth, mobile tongue, oropharynx, or in any erythroplakia lesion)or Mild, moderate, or severe dysplasia at any site of the oral cavity or oropharynx within the lesion
Able to be assessed by bi-directional measurements
Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2
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
White Blood Cells (WBC) > 3,000/mm^3
Platelet count > 125,000/mm^3
Bilirubin, Aspartate aminotransferase (AST) and Alanine transaminase (ALT) < 1.5 times upper limit of normal (ULN)
Blood Urea Nitrogen (BUN) and Creatinine < 1.5 times ULN

Exclusion Criteria:

Pregnant or nursing
Positive pregnancy test (Fertile patients must use effective barrier contraception)
Contraindication to thiazolidinediones (and prior use of)
Allergy to pioglitazone or other thiazolidinediones
Serious oral infection
Invasive carcinoma within the past 60 months except nonmelanoma skin cancer or carcinoma in situ of the cervix
Concurrent malignancy
Less than 3 months since prior chemopreventative agents, biologic or immunologic therapy or experimental therapy
Less than 3 months since prior megadose vitamins or alternative therapy
Concurrent pharmacologic treatment for diabetes
Concurrent chronic use of non-steroidal anti-inflammatory drugs is allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00099021

Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Frank G. Ondrey, MD, PhD

Masonic Cancer Center, University of Minnesota

More Information

Additional Information:

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Frank Ondrey, M.D., Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00099021 History of Changes
Other Study ID Numbers:	CDR0000393562, UMN-0109M07254, UMN-2001LS068
Study First Received:	December 8, 2004
Results First Received:	October 13, 2009
Last Updated:	April 13, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:

lip and oral cavity cancer
oropharyngeal cancer
oral leukoplakia

Additional relevant MeSH terms:

Neoplasms
Disease
Head and Neck Neoplasms
Leukoplakia
Leukoplakia, Oral
Precancerous Conditions
Pathologic Processes
Neoplasms by Site

Pathological Conditions, Anatomical
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012