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

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.

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).