Pioglitazone to Treat Adults Undergoing Surgery for Non-small Cell Lung Cancer
Condition: Non-Small-Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pioglitazone
Intervention description: 45 mg tablet daily by mouth for six weeks
Intervention MeSH terms: Pioglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC Stage Ia-IIb; Resectable NSCLC; Non-Small Cell Lung Cancer; NSCLC

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:

        1. Medical history, physical examination, blood tests, electrocardiogram

        2. 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.

        3. 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.

        4. 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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. 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.

               2. Age greater than or equal to 18 years of age.

               3. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal
                  to 2.

               4. Patients must have the capacity and willingness to sign a written informed
                  consent and demonstrate willingness to comply with an oral regimen.

               5. 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.

               6. 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

             7. Patients must agree to swallow oral tablets.

             8. 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.

             9. Females are eligible to participate in the study if

          -  She is of non-childbearing potential as defined by having had a hysterectomy, a
             bilateral oophorectomy, a bilateral tubal ligation, or having been post-menopausal for
             greater than or equal to 1 year.

          -  She is of childbearing potential and has a negative pregnancy test within 2 weeks of
             the starting the study drug and agrees to the use of non-hormonal methods of birth
             control, e.g., barrier methods, for the duration of the study due to possible drug
             interactions.

        EXCLUSION CRITERIA:

          1. Pregnant or lactating women.

          2. 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.

          3. Patients with greater than or equal to class II New York Heart Association (NYHA)
             congestive heart failure or history of congestive heart failure.

          4. Patients with greater than or equal to grade 2 (moderate) edema.

          5. Patients with diabetes mellitus being treated with insulin or any pharmacologic
             therapy.

          6. Patients taking gemfibrozil or rifampin, due to drug interactions with pioglitazone.

          7. 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.