A Randomized Phase II Study of SUBATM-itraconazole in Patients With Untreated Squamous NSCLC. (NA_00067809)

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).