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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00099021

Enrollment

Registered

2004-12-09

Start date

2003-06-30

Completion date

2008-06-27

Last updated

2022-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Head and Neck Cancer, 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 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.

Interventions

DRUGpioglitazone hydrochloride

Given PO

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Patients' Overall Response	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

Secondary

Measure	Time frame	Description
Patients' Clinical Response	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	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.

Other

Measure	Time frame	Description
Cyclin D1 and p21 Immune Histochemistry	Pre (Day 0) and Post (Week 12) Treatment	Immune histochemistry / tissue staining for a possible biomarker.
Cyclooxygenase-2 Staining	Pre (Day 0) and Post (Week 12) Treatment	Immune histochemistry / tissue staining for a possible biomarker.
Piogliotazone Gamma Immune Histochemistry	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	Pre (Day 0) and Post (Week 12) Treatment	Quantitative studies of serum and saliva components for a pre and post treatment possible biomarker.
Apotosis (Cell Death)	Pre (Day 0) and Post (Week 12) Treatment	Immune histochemistry / tissue staining for a possible biomarker.
Nf Kappa B p65	Pre (Day 0) and Post (Week 12) Treatment	Immune histochemistry / tissue staining for a possible biomarker.
Ki 67 Labeling Index	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	Pre (Day 0) and Post (Week 12) Treatment	Immune histochemistry / tissue staining for a possible biomarker.
Involucrin and Transglutaminase Staining	Pre (Day 0) and Post (Week 12) Treatment	Immune histochemistry / tissue staining for a possible biomarker.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Pioglitazone Patients Patients with measurable leukoplakia who received all study medication (oral pioglitazone once daily for 12 weeks) and completed the trial.	21
Total	21

Baseline characteristics

Characteristic	Pioglitazone Patients
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	19 Participants
Age, Continuous	56.1 years
Region of Enrollment United States	21 participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	9 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	18 / 21
serious Total, serious adverse events	0 / 21

Outcome results

Primary

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

Time frame: Week 16 (4 weeks post dose)

Arm	Measure	Group	Value (NUMBER)
Pioglitazone Patients	Patients' Overall Response	Complete Response	0 Participants
Pioglitazone Patients	Patients' Overall Response	Partial Response	15 Participants
Pioglitazone Patients	Patients' Overall Response	Stable Disease	2 Participants
Pioglitazone Patients	Patients' Overall Response	Progressive Disease	4 Participants
Pioglitazone Patients	Patients' Overall Response	Partial + Complete Response	15 Participants

Secondary

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

Time frame: Week 16 (4 weeks post dose)

Arm	Measure	Group	Value (NUMBER)
Pioglitazone Patients	Patients' Clinical Response	Complete Response	3 Participants
Pioglitazone Patients	Patients' Clinical Response	Partial Response	14 Participants
Pioglitazone Patients	Patients' Clinical Response	Stable Disease	4 Participants
Pioglitazone Patients	Patients' Clinical Response	Progressive Disease	0 Participants
Pioglitazone Patients	Patients' Clinical Response	Partial + Complete	17 Participants

Secondary

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.

Time frame: Week 16 (4 weeks post dose)

Arm	Measure	Group	Value (NUMBER)
Pioglitazone Patients	Patients' Histological (Tissue) Response	Partial Response	2 Participants
Pioglitazone Patients	Patients' Histological (Tissue) Response	Stable Disease	14 Participants
Pioglitazone Patients	Patients' Histological (Tissue) Response	Complete Response	1 Participants
Pioglitazone Patients	Patients' Histological (Tissue) Response	Progressive Disease	4 Participants
Pioglitazone Patients	Patients' Histological (Tissue) Response	Partial + Complete Response	3 Participants

Other Pre-specified