Itraconazole and Pemetrexed Disodium in Treating Patients With Previously Treated Non-Small Cell Lung Cancer

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IISupportive care, TreatmentOver 18J0881
NCI-2010-02070, NCT00769600

Trial Description

Summary

This randomized phase II trial is studying how well giving itraconazole together with pemetrexed disodium to see how well it works compared to pemetrexed disodium alone in treating patients with previously treated non-small cell lung cancer (NSCLC). Itraconazole may stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving itraconazole together with pemetrexed disodium may be a better way to block tumor growth.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the 3-month event-free survival of the combination of itraconazole and pemetrexed (pemetrexed disodium) in patients with previously treated non-squamous non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To determine the objective response rate of the combination of itraconazole and pemetrexed in patients with previously treated non-squamous non-small cell lung cancer.

II. To assess the changes in tumor-associated blood flow and tumor metabolic activity in patients with previously treated non-squamous non-small cell lung cancer receiving pemetrexed alone or pemetrexed plus itraconazole.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive itraconazole orally (PO) once daily on days 1-21 and pemetrexed disodium intravenously (IV) over 10 minutes on day 1.

ARM II: Patients receive pemetrexed disodium IV as in arm I.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 8 weeks.

Eligibility Criteria

Inclusion Criteria:

Patients must have received at least one previous chemotherapy regimen for NSCLC

Life expectancy of greater than 12 weeks

Leukocytes >= 3,000/mcL

Absolute neutrophil count >= 1,500/mcL

Platelets >= 100,000/mcL

Total bilirubin within normal institutional limits

Patients must have histologically or cytologically confirmed non-squamous NSCLC

Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

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 computed tomography (CT) scan

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal

Creatinine clearance >= 45 mL/min adjusted per institutional guidelines

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:

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

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

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 (except for alopecia, fatigue, and grade 1 neurologic toxicity)

Patients may not be receiving any other investigational agents

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; in addition, itraconazole depends on gastric acidity for absorption; per the itraconazole package insert, in patients taking an H2 blocker, itraconazole absorption was normalized by co-administration with 8 ounces of a cola beverage; patients on a daily gastric acid blocker are encouraged to take the itraconazole with an 8 ounce cola beverage; also per the package insert, antacids should be administered at least 1 hour before or 2 hours after administration of itraconazole

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

Human immunodeficiency virus (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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Johns Hopkins University/Sidney Kimmel Cancer Center

  • National Cancer Institute
Charles Michael Rudin, Principal Investigator

Trial Sites

U.S.A.

Maryland
Baltimore

Johns Hopkins University/Sidney Kimmel Cancer Center

Charles Michael Rudin
Ph: 410-502-0678
Email: rudin@jhmi.edu

Charles Michael Rudin
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00769600

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.