This phase I trial studies the side effects and best dose of exemestane in combination with pemetrexed disodium and carboplatin in treating post-menopausal women with stage IV non-small cell lung cancer. Exemestane may stop the growth of tumor calls by blocking some of the enzymes need for cell growth. Drugs used in chemotherapy, such as pemetrexed disodium and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving exemestane together with pemetrexed disodium and carboplatin may kill more tumor cells
PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of escalating doses of exemestane when given with pemetrexed (pemetrexed disodium) and carboplatin in post-menopausal women with stage IV non-squamous, non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. Determine the objective tumor response rate (defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) in patients treated with pemetrexed, carboplatin and exemestane. II. Evaluate the pharmacokinetic profile of pemetrexed, carboplatin and exemestane. III. Evaluate quality of life in patients treated with pemetrexed, carboplatin and exemestane. IV. Analyze tumor tissue biomarkers for potential correlation with response. OUTLINE: This is a dose-escalation study of exemestane. Patients receive exemestane orally (PO) once daily (QD) on days 1-28 and pemetrexed disodium intravenously (IV) over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Given PO
Given IV
Given IV
Correlative studies
Correlative studies
Ancillary studies
Ancillary studies
Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Tabulation, grading, and attribution of serious adverse events (SAEs) and adverse events (AEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: Up to 3 years
Proportion achieving clinical response
For categorical markers Fisher's exact test will be used. The log rank test will be used to examine association between categorical markers and time to disease progression. For quantitative markers one-way ANOVA will be used. Cox-proportional hazards regression models will be used to correlate quantitative markers with time to disease progression. Pearson correlations will be used between pairs of quantitative markers. If there is significant non-normality the Kendall correlation coefficients will be used. Mixed effects models will be used to quantify markers at multiple time points.
Time frame: Up to 3 years
Quality of life in patients treated with pemetrexed disodium, carboplatin and exemestane
Quality of life measures will be compared between response categories (ANOVA) and the effect of time on therapy will be assessed with mixed effects models.
Time frame: Up to 3 years
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