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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Patients' Overall Response [ Time Frame: Week 16 (4 weeks post dose) ]

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



Original Primary Outcome:

Current Secondary Outcome:

  • Patients' Clinical Response [ Time Frame: Week 16 (4 weeks post dose) ]
    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) ]
    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 ]
    Immune histochemistry / tissue staining for a possible biomarker.
  • Ki 67 Labeling Index [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ]
    Immune histochemistry / tissue staining for a possible biomarker.
  • Apotosis (Cell Death) [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ]
    Immune histochemistry / tissue staining for a possible biomarker.
  • Pigliotazone Gamma Immune Histochemistry [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ]
    Immune histochemistry / tissue staining for a possible biomarker.
  • Cyclooxygenase-2 Staining [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ]
    Immune histochemistry / tissue staining for a possible biomarker.
  • Cyclin D1 and p21 Immune Histochemistry [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ]
    Immune histochemistry / tissue staining for a possible biomarker.
  • Involucrin and Transglutaminase Staining [ Time Frame: Pre (Day 0) and Post (Week 12) Treatment ]
    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 ]
    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 ]
    Quantitative studies of serum and saliva components for a pre and post treatment possible biomarker.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 8, 2004
Date Started: June 2003
Date Completion:
Last Updated: December 28, 2016
Last Verified: December 2016