Phase II Study of Itraconazole and Pemetrexed in Patients With Previously Treated Non-Squamous NSCLC
Condition: Recurrent Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Itraconazole; Pemetrexed
Intervention description: Itraconazole 200 mg once daily; Pemetrexed every 21 days.
Intervention MeSH terms: Itraconazole; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Recurrent Non-Small Cell Lung Cancer

Summary:

      Primary Objective

      To evaluate the 3-month event-free survival of the combination of the combination of
      itraconazole and pemetrexed in patients with recurrent/refractory non-small cell lung cancer.

      Secondary Objectives

      To determine the objective response rate of the combination of itraconazole and pemetrexed in
      patients with recurrent/refractory non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed NSCLC.

          -  Patient must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >20
             mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for
             the evaluation of measurable and non-measurable disease.

          -  Patients must have received at least one previous chemotherapy regimen and have
             recurrent or refractory disease.

          -  Age >18 years. Because no dosing or adverse event data are currently available on the
             use of itraconazole in combination with pemetrexed in patients < 18 years of age, such
             patients are excluded from this study but will be eligible for future pediatric phase
             2 combination trials.

          -  Life expectancy of greater than 12 weeks.

          -  ECOG performance status < 2 (Karnofsky > 60%; see Appendix A).

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocyte > 3,000/mcL

               -  absolute neutrophil count > 1,500/mcL

               -  platelets > 100,000/mcL

               -  total bilirubin within normal institutional limits

               -  AST(SGOT)/ALT(SGPT)< 2.5 X institutional upper limit of normal

               -  creatinine within normal institutional limits

               -  creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels
                  above institutional normal

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and 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 treating physician
             immediately.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 2 weeks earlier.

          -  Patients may not be receiving any other investigational agents.

          -  Patients who have received prior pemetrexed chemotherapy.

          -  Patients with uncontrolled brain metastases. Patients with brain metastases must have
             stable neurologic status following local therapy (surgery or radiation) for at least 2
             weeks, and must be without neurologic dysfunction that would confound the evaluation
             of neurologic and other adverse events.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to itraconazole and pemetrexed or other agents used in the study.

          -  Itraconazole is a strong CYP3A4 inhibitor and may increase plasma concentrations of
             drugs metabolized by this pathway. Coadministration of cisapride, midazolam, pimozide,
             quinidine, lovastatin, simvastatin, triazolam, dofetilide, or levacetylmethadol
             (levomethadyl) with itraconazole is contraindicated. Patients who take any of these
             medications and who are not able to change to an alternative medication will be
             excluded. Lists including medications and substances known or with the potential to
             interact with the CYP3A4 isoenzymes are provided in Section 7.1.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because itraconazole and pemetrexed are
             Class C and D agents, respectively, with the potential for teratogenic or
             abortifacient effects. Because there is an unknown but potential risk for adverse
             events in nursing infants secondary to treatment of the mother with itraconazole and
             pemetrexed, breastfeeding should be discontinued if the mother is treated with
             itraconazole or pemetrexed. These potential risks may also apply to other agents used
             in this study.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with itraconazole or pemetrexed. In
             addition, these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated.