NCT00923949

Brief Summary

Background:

  • Pioglitazone is a drug that belongs to the class of antidiabetic agents called thiazolidinediones. It is approved for treatment of type 2 diabetes mellitus.
  • Research suggests that the thiazolidinediones may have anticancer activity that can reduce cancer risk or cause tumors to shrink. Objectives:
  • To test how a pioglitazone works as a treatment of Stage IA to IIB Non-Small Cell Lung Cancer (NSCLC) and to look at the effect of the drug on cancer cells. Eligibility:
  • Patients 18 years of age or older who will undergo surgery for Stage IA to IIB non-small cell lung cancer (NSCLC). Design:
  • The study includes a screening visit to determine eligibility, treatment with pioglitazone, a follow-up visit after 2 to 3 weeks of treatment and a post-surgery visit. Procedures include:
  • Medical history, physical examination, blood tests, electrocardiogram
  • Bronchoscopy to obtain cancer cells. This is done before pioglitazone treatment begins and again during lung surgery. Some patients may also require mediastinoscopy or biopsy to collect cells.
  • Treatment with pioglitazone tablets once a day for at least 2 weeks and no more than 6 weeks, depending on when surgery has been scheduled.
  • Positron emission tomography (PET) scan before starting pioglitazone treatment. National Cancer Institute (NCI) patients also have a follow-up PET scan after treatment but before surgery.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2008

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2008

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

June 17, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 18, 2009

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2010

Completed
2 years until next milestone

Results Posted

Study results publicly available

February 14, 2012

Completed
Last Updated

September 30, 2015

Status Verified

February 1, 2012

Enrollment Period

1.6 years

First QC Date

June 17, 2009

Results QC Date

January 11, 2012

Last Update Submit

September 29, 2015

Conditions

Non-Small-Cell Lung Cancer

Keywords

NSCLC Stage Ia-IIbResectable NSCLCNon-Small Cell Lung CancerNSCLC

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With a Change in Ki-67 Due to the Effect of Pioglitazone in Tumor Tissue

    Antigen ki-67 (Ki-67) will be assessed by immunohistochemistry.

    58 days

Secondary Outcomes (6)

  • Number of Participants With Effects of Pioglitazone on Multiple Biomarkers in Tumor

    58 days

  • Number of Participants With Adverse Events

    58 days

  • Number of Participants With Metabolic Activity Determined by Fludeoxyglucose Positron-emission Tomography (FDG-PET)

    58 days

  • Number of Participants With Effects of Pioglitazone on Premalignant Tissue Biomarkers

    58 days

  • Number of Participants With Effects of Pioglitazone on Histologically Normal Tissue Biomarkers

    58 days

  • +1 more secondary outcomes

Study Arms (1)

Pioglitazone

EXPERIMENTAL

45 mg tablet daily by mouth for six weeks

Drug: Pioglitazone

Interventions

PioglitazoneDRUG

45 mg tablet daily by mouth for six weeks

Pioglitazone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients with newly diagnosed stage Ia-IIb resectable non-small cell lung cancer who will be undergoing definitive surgery. If histologic confirmation of lung cancer has not previously been made, the baseline study bronchoscopy, as outlined in section 3.6.2, or computed tomography (CT)-guided biopsy with tissue saved for protocol use may be used to document NSCLC, after obtaining informed consent. Should the bronchoscopy or CT-guided biopsy be negative for non-small cell lung cancer (NSCLC), the patient will be taken off study prior to drug treatment. At National Cancer Institute (NCI), histologic confirmation of the diagnosis will be performed by the NCI Laboratory of Pathology.
  • Age greater than or equal to 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
  • Patients must have the capacity and willingness to sign a written informed consent and demonstrate willingness to comply with an oral regimen.
  • The time between initial diagnosis and the scheduled surgery date allow for the subject to receive a minimum of 2 weeks or a maximum of 6 weeks treatment with pioglitazone. The maximum time between enrollment on this trial and surgery will be 6-weeks and there will be no delay between the end of pioglitazone treatment and surgery.
  • Patients must have normal organ and marrow function as defined below:
  • absolute neutrophil count greater than or equal to 1,500/mL
  • hemoglobin greater than 10 g/dL
  • platelets greater than or equal to 100,000/mL
  • Bilirubin less than 1.8 mg/dL
  • aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 1.5 times upper limits of institutional normal
  • creatinine less than 1.5 times upper limit of institutional normal
  • \. Patients must agree to swallow oral tablets.
  • \. Patients who will agree to undergo two bronchoscopies as detailed in section 3.6.2 (before treatment and at the time of surgery).
  • For those patients who are undergoing mediastinoscopy as part of their standard-of-care, the pre-treatment bronchoscopy may be performed during the mediastinoscopy. If the patient remains eligible for definitive surgical resection after the mediastinoscopy, the patient may begin pioglitazone treatment on this protocol.
  • +3 more criteria

You may not qualify if:

  • Pregnant or lactating women.
  • Patients who are undergoing chemotherapy, treatment with biologic agents, or radiation therapy. Prior chemotherapy, biologic agent treatment, or radiation therapy, greater than 1 year ago, is allowed.
  • Patients with greater than or equal to class II New York Heart Association (NYHA) congestive heart failure or history of congestive heart failure.
  • Patients with greater than or equal to grade 2 (moderate) edema.
  • Patients with diabetes mellitus being treated with insulin or any pharmacologic therapy.
  • Patients taking gemfibrozil or rifampin, due to drug interactions with pioglitazone.
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active liver disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

New York University

New York, New York, 10016, United States

Location

Related Publications (3)

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

    PMID: 17237035BACKGROUND

  • Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP. Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8806-11. doi: 10.1073/pnas.95.15.8806.

    PMID: 9671760BACKGROUND

  • Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB, Holden SA, Chen LB, Singer S, Fletcher C, Spiegelman BM. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med. 1998 Sep;4(9):1046-52. doi: 10.1038/2030.

    PMID: 9734398BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

Study never published; terminated early due to low accrual.

Results Point of Contact

Title
Giuseppe Giaccone M.D.
Organization
National Cancer Institute
giacconeg@mail.nih.gov
301-496-4916

Study Officials

  • Giuseppe Giaccone, M.D.

    National Cancer Institute (NCI)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH

Study Record Dates

First Submitted

June 17, 2009

First Posted

June 18, 2009

Study Start

August 1, 2008

Primary Completion

March 1, 2010

Study Completion

March 1, 2010

Last Updated

September 30, 2015

Results First Posted

February 14, 2012

Record last verified: 2012-02

Locations

US(2)