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Note: This record shows only the 20 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 19 October 2017
Main ID:  NCT00951379
Date of registration: 31/07/2009
Prospective Registration: Yes
Primary sponsor: National Cancer Institute (NCI)
Public title: Pioglitazone for Oral Premalignant Lesions
Scientific title: Phase IIB Randomized, Placebo Controlled Trial of Pioglitazone for Oral Premalignant Lesions an Inter-consortium Collaborative Study
Date of first enrolment: February 2010
Target sample size: 52
Recruitment status: Terminated
URL:  https://clinicaltrials.gov/show/NCT00951379
Study type:  Interventional
Study design:   
Phase:  Phase 2
Countries of recruitment
Canada Italy United States
Contacts
Name:   Powel H. Brown
Address: 
Telephone:
Email:
Affiliation:  University of Texas MD Anderson Cancer Center, Consortium PI
Key inclusion & exclusion criteria

Inclusion Criteria:

- STAGE I:

- Males or females with a suspected or histologically confirmed oral premalignant
lesion(s) (up to three target lesions may be followed for the purpose of the study)
that has a length (longest diameter) of 8 mm or greater and width (diameter
perpendicular to greatest length) of 3 mm or greater in size

- If a participant has had a biopsy of the target oral premalignant lesions (OPL)
lesion(s) within 6 weeks prior to the screening visit and archival tissue is
available and the participant agrees to have archival tissue used for histologic
confirmation and biomarker analysis, then NO additional biopsies (of the OPL)
need to be performed at the screening visit; the pre-screening biopsy must
undergo centralized pathology review before the second stage of registration can
be performed; if archival tissue is not available, a waiting period of 6 weeks
from the time of the last biopsy must be observed before re-biopsy for study
purposes

- If a participant has not had a biopsy of the suspected OPL at the time of the
screening visit, then a biopsy of the lesion must be performed during the
screening visit; the screening biopsy must undergo centralized pathology review
before the second stage of registration can be performed

- The participant's life expectancy is > 6 months

- The participant has discontinued any other oral cancer chemopreventive therapy at
least 12 weeks prior to the baseline visit and all toxicities have been fully
resolved; daily aspirin is permitted

- The participant is willing and able to fully participate for the duration of the study

- Women must not be pregnant or lactating; women of child-bearing potential (women are
considered not of childbearing potential if they are at least two years postmenopausal
and/or surgically sterile) must have used adequate contraception (abstinence; barrier
methods such as IUD, diaphragm with spermicidal gel, condom, or others; and hormonal
methods such as birth control pills or others) since her last menses prior to study
entry; women of child-bearing potential and men must agree to use adequate
contraception for the duration of study participation; should a woman become pregnant
or suspect she is pregnant while participating in this study, she should inform her
study physician immediately

- Ability to understand and the willingness to sign a written informed consent document

- STAGE II:

- The participant has one or more target lesions histologically confirmed by a biopsy
obtained no more than 9 weeks prior to randomization, that is either:

- An EARLY premalignant lesion defined to be at high risk:

- Mild dysplasia of any site

- Hyperplastic leukoplakia of a high-risk site

- Dorsal, lateral or ventral tongue

- Floor of mouth

- An ADVANCED premalignant lesion defined as the presence of at least one of the
following:

- Moderate dysplasia

- Severe dysplasia (excluding carcinoma in situ)

- Erythroplakia (due to the high risk for progression associated with
erythroplakia, erythroplakia of any histology will be defined as an ADVANCED
oral premalignant lesion)

- Hemoglobin levels equal to or above the lower limit of normal

- White blood cells >= 3,000/uL

- Platelets >= 125,000/uL

- Total bilirubin =< 1.5 * upper limit of normal (ULN)

- BUN and serum creatinine =< 1.5 * ULN

- Glucose, serum < 200 mg/dL

- The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0 or
1

- If the participant is female and of childbearing potential and not lactating she has a
documented negative serum pregnancy test within 14 days prior to randomization

- The participant has a baseline EKG that does not show signs of acute cardiac ischemia
or cardiac dysrhythmia (except for 1st degree AV block or chronic atrial
fibrillation); EKG can be an earlier report within 12 weeks prior to registration

- Participants using the drugs listed below may not be randomized unless they are
willing to stop the medications (and possibly change to alternative non-excluded
medications to treat the same conditions) no less than 3 days prior to starting
pioglitazone or placebo on this study; the use of the following drugs or drug classes
is prohibited during pioglitazone/placebo treatment: participants taking inhibitors of
CYP2C8 (gemfibrozil, ketoconazole, quercetin, trimethoprim), enzyme inducers of CYP2C8
(cortisol, dexamethasone, phenobarbital, rifampin), and CYP3A4 substrate

Exclusion Criteria:

- The participant has active cancer or carcinoma in situ of the head and neck

- The participant has a contraindication to biopsy

- The participant has presence of congestive heart failure (New York Heart Association
(NYHA) class II-IV), uncontrolled hypertension (systolic > 150 or diastolic > 100), or
unstable angina

- The participant has any history of congestive heart failure or history of myocardial
infarction within the past 6 months

- The participant exhibits clinical evidence of active liver disease or history of
chronic liver disease

- The participant has > Common Terminology Criteria for Adverse Events (CTCAE) grade 1
edema

- The participant has known diabetes and is on insulin or oral agents; the participant
is receiving medical therapy for dysregulated blood sugar

- The participant who currently receives an enzyme inhibitor of CYP2C8 (gemfibrozil,
ketoconazole, quercetin, trimethoprim), or enzyme inducer of CYP2C8 (cortisol,
dexamethasone, phenobarbital, rifampin), or CYP3A4 substrate will not be eligible for
randomization after assessing eligibility in stage two unless he/she will not be
eligible for randomization after assessing eligibility in stage two unless he/she is
willing to stop these drugs and possibly replace them with alternative therapies

- The participant currently receives pregabalin or thioridazine

- The participant has experienced jaundice with Rezulin (troglitazone)

- The participant has a history of colorectal cancer, familial adenomatous polyposis
(FAP) or hereditary non-polyposis colorectal cancer (HNPCC)

- The participant has a history of bladder cancer or in situ bladder cancer

- The participa



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Oral Leukoplakia
Intervention(s)
Drug: Pioglitazone hydrochloride
Other: laboratory biomarker analysis
Other: placebo
Primary Outcome(s)
Dichotomized Clinical Response: Participant Complete or Partial Response Defined as =/>50% Reduction in the Sum of the Measured Products of Perpendicular Dimensions of the Target Lesion(s) or Improvement in the Degree of Dysplasia or Hyperplasia [Time Frame: Response assessed at Week 24 ±1 Week]
Dichotomized Histologic Response (HR): Participant Complete or Partial Response Defined as =/>50% Reduction in the Sum of the Measured Products of Perpendicular Dimensions of the Target Lesion(s) or Improvement in the Degree of Dysplasia or Hyperplasia [Time Frame: Response assessed at Week 24 ±1 Week]
Overall Response [Time Frame: Response assessed at Week 24 ±1 Week]
Secondary Outcome(s)
Biomarker Measurements at Scheduled Visits: Tissue Levels of B-cell Lymphoma 2 (Bcl2) [Time Frame: Baseline to end of study, 24 weeks]
Biomarker Measurements at Scheduled Visits: Tissue Levels of Cyclin D1 [Time Frame: Baseline to end of study, 24 weeks]
Biomarker Measurements at Scheduled Visits: Tissue Levels of Ki-67 [Time Frame: Baseline to end of study, 24 weeks]
Biomarker Measurements at Scheduled Visits: Tissue Levels of p21 [Time Frame: Baseline to end of study, 24 weeks]
Biomarker Measurements at Scheduled Visits: Tissue Levels of PPARG Nucleus and PPARG Cytoplasm [Time Frame: Baseline to end of study, 24 weeks]
Number of Participant With Clinical Response by Baseline Characteristics: Alcohol Use [Time Frame: Up to 26 weeks]
Number of Participant With Clinical Response by Baseline Characteristics: Tobacco Use [Time Frame: Up to 26 weeks]
Number of Participants Affected by Adverse Events Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0) [Time Frame: Up to 26 weeks]
Number of Participants With >5.0 mg/L in Level of C-reactive Protein in Plasma [Time Frame: Baseline to end of study, 24 weeks]
Number of Participants With Level of C-reactive Protein in Plasma Decrease From >5.0 mg/L to <= 5.0 mg/L From Baseline to End of Study [Time Frame: Baseline to end of study, 24 weeks]
Secondary ID(s)
INC07-10-01
MDA-2009-0339
N01CN35153
N01CN35159
NCI-2012-03152
P30CA016672
UWI H-2009-0106
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
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