This randomized phase II trial studies how well pemetrexed disodium with or without erlotinib hydrochloride works in treating patients with stage IIIB-IV or recurrent non-small cell lung cancer. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium is more effective with or without erlotinib hydrochloride in treating non-small cell lung cancer.
PRIMARY OBJECTIVES: I. To evaluate progression free survival (PFS) in the schedule-modulated concomitant administration of erlotinib (erlotinib hydrochloride) and pemetrexed (pemetrexed disodium), and in single agent pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) as second-line chemotherapy. SECONDARY OBJECTIVES: I. To evaluate antitumor objective response rate (complete response \[CR\] + partial response \[PR\]) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. II. To evaluate disease control rate (response rate + stable disease, i.e., CR+PR+ stable disease \[SD\]) and duration of response. III. To evaluate median time to progression (TTP) and overall survival (OS). IV. To evaluate the safety profile of concurrent pemetrexed and erlotinib versus single agent pemetrexed. TERTIARY OBJECTIVES: i. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of pemetrexed and erlotinib. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive pemetrexed disodium IV as in Arm A and erlotinib hydrochloride orally (PO) once daily (QD) on days 2-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
79
Given PO
Correlative studies
Given IV
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
University of Massachusetts Memorial Health Care
Worcester, Massachusetts, United States
Albert Einstein College of Medicine
The Bronx, New York, United States
Bronx River Medical Associates PC
The Bronx, New York, United States
Eastchester Center for Cancer Care
The Bronx, New York, United States
PFS (Progression Free Survival)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Time from randomization until documented tumor progression or death from any cause, assessed up to 12 months
Objective Response Rate (CR +PR) Evaluated Using RECIST
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Response rates in each arm will be summarized by computing proportions and corresponding 95% confidence intervals.
Time frame: Up to 12 months
Overall Survival
Time to event endpoints will be analyzed using standard survival analytic methods, including the Kaplan-Meier approach for estimating the survival distributions.
Time frame: Time from the date of randomization to date of death due to any cause, assessed up to 12 months
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