A Randomized Phase II Study of SUBATM-itraconazole in Patients With Untreated Squamous NSCLC.
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Interventions
- Registration Number
- NCT01752023
- Brief Summary
Response rates.
Changes in tumor blood flow.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cisplatin + Gemcitabine Cisplatin + Gemcitabine Arm B = Cisplatin 75 mg/m2 day 1, Gemcitabine 1000 mg/m2 days 1 + 8 for 6 cycles. Then Best supportive care. Cisplatin + Gemcitabine with SUBATM-itraconazole Cisplatin + Gemcitabine with SUBATM-itraconazole SUBATM-itraconazole 200 mg BID, Cisplatin 75 mg/m2 day 1, Gemcitabine 1000 mg/m2 days 1 + 8 for 6 cycles. Then SUBATM-itraconazole 200 mg BID alone.
- Primary Outcome Measures
Name Time Method Tumor Blood Flow. 6 weeks. 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.
Objective Response Rates 6 weeks Per response evaluation criteria in solid tumors criteria
- Secondary Outcome Measures
Name Time Method Median Time to Progression 2 years. To determine the median time to progression and median duration of survival of patients with metastatic squamous non-small cell lung cancer treated with cisplatin and gemcitabine with or without SUBATM-itraconazole.
Adverse Effects 2 years. To characterize the adverse effects of cisplatin and gemcitabine with or without SUBATM-itraconazole in this patient population.
Itraconazole Exposure Parameters 2 years. To correlate itraconazole exposure parameters with median time to progression and median survival in this patient population.
Tumor Necrosis 2 years. To assess changes in tumor necrosis in response to cisplatin and gemcitabine with or without SUBATM-itraconazole.
Trial Locations
- Locations (2)
Bayview Medical Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University, SKCCC
🇺🇸Baltimore, Maryland, United States