a randomized phase ii study of subatm-itraconazole in patients with untreated squamous nsclc.

Conditions: Non-small Cell Lung Cancer Metastatic

Summary: response rates. changes in tumor blood flow.

to determine the objective response rates of cisplatin and gemcitabine with or without subatm-itraconazole in patients with chemotherapy-naïve metastatic squamous non-small cell lung cancer. to assess the changes in tumor blood flow as measured by contrast enhanced mri scanning in patients with metastatic squamous non-small cell lung cancer treated with cisplatin and gemcitabine with or without subatm-itraconazole.

Eligibility criteria:
inclusion criteria: * stage iv squamous cell lung cancer, with no prior systemic chemotherapy. * patients who have received prior adjuvant chemotherapy for early-stage lung cancer are eligible if at least 6 months have elapsed from completion of that treatment. * patients whose tumors contain mixed non-small cell histologies are eligible if squamous carcinoma is the predominant histology. mixed tumors with small cell anaplastic elements are not eligible. * patient must have measurable disease per recist 1.1 (defined in section 9.1.2). * patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the recurrence is outside the original radiation therapy port. radiation therapy must have been completed greater than or equal to 2 weeks prior to enroll in this study. * age greater than or equal to 18 years. because no dosing or adverse event data are currently available on the use of itraconazole or subatm-itraconazole in combination with gemcitabine/cisplatin in patients under 18 years of age, such patients are excluded from this study. squamous cell lung cancer is exceedingly rare in children. * life expectancy of at least 12 weeks. * eastern cooperative oncology group performance status 0 - 1. * patients must have adequate organ and marrow function. * 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: * prior treatment with gemcitabine, cisplatin (except in the adjuvant setting), itraconazole or subatm-itraconazole. * 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, subatm-itraconazole, gemcitabine, cisplatin or other agents used in the study. * itraconazole is a strong cyp3a4 inhibitor and may increase plasma concentrations of drugs metabolized by this pathway. co-administration of cisapride, midazolam, pimozide, quinidine, lovastatin, simvastatin, triazolam, dofetilide, or levacetylmethadol (levomethadyl) with subatm-itraconazole or itraconazole is contraindicated. * 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 is class c agent and both gemcitabine and cisplatin are class d agents, 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 subatm-itraconazole and gemcitabine/cisplatin, breastfeeding should be discontinued if the mother is to be treated on this protocol. * hiv-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with subatm-itraconazole, gemcitabine, or cisplatin with these essential mediations. * medical contra-indication to mri (e.g. gadolinium allergy, or severe claustrophobia).