A Randomized Phase II Study of SUBATM-itraconazole in Patients With Untreated Squamous NSCLC.
Condition: Non-small Cell Lung Cancer Metastatic
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Cisplatin + Gemcitabine with SUBATM-itraconazole; Cisplatin + Gemcitabine
Intervention description: Experimental Arm; Active Comparator
Intervention MeSH terms: Itraconazole; Hydroxyitraconazole; Cisplatin; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      Response rates.

      Changes in tumor blood flow.
    

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).