Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. This phase II trial is studying how well lapatinib works in treating brain metastases in patients with stage IV breast cancer and brain metastases.
PRIMARY OBJECTIVES: I. To evaluate the objective response rate in the central nervous system (CNS) (complete plus partial responses), as assessed by standard MRI, to oral GW572016 among patients with progressive brain metastases from HER2-positive breast cancer. SECONDARY OBJECTIVES: I. To evaluate the site of first failure (CNS, extra-CNS, both, or death) and overall survival of patients treated with GW572016 for brain metastases. II. To evaluate the overall objective response rate (complete plus partial response) and time to first progression at any site. III. To assess quality of life (QOL), neurologic QOL, and cause of death in patients treated with GW572016 for brain metastases. IV. To determine the qualitative and quantitative toxicities associated with oral GW572016, given at a dose of 750 mg orally, twice daily. V. To evaluate the sensitivity of PET with dedicated brain sequences to detect brain metastases from breast cancer. VI. To explore the relationship between decline in PET uptake at 1 week and decline in PET uptake at 8 weeks. VII. To characterize the vessel patterns seen on MRI at baseline, 8 weeks, and 16 weeks of treatment with GW572016. VIII. To describe changes in serum HER2 ECD over time. IX. To describe the baseline EGFR, HER2, IGF-IR, and degree of HER2 gene amplification in primary tumor blocks. OUTLINE: This is an open-label, multicenter study. Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at 8 weeks. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 0.5-1.5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Given orally
Correlative studies
Ancillary studies
Ancillary studies
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Objective response rate defined as the percentage of patients with a complete response (CR) or partial response (PR) in the CNS
A 95% confidence interval (CI) for percent of patients with CNS response will be calculated if the study does not terminate accrual early. The method of Atkinson and Brown will be used to calculate the CI conditional on the sequential design.
Time frame: Up to 5 years
Objective response in non-CNS sites
A 95% CI for percent of patients with CNS response will be calculated if the study does not terminate accrual early. The method of Atkinson and Brown will be used to calculate the CI conditional on the sequential design.
Time frame: Up to 5 years
Site of first progression
Time frame: At the time of disease progression
Time to progression (TTP)
The time to progression will be summarized using a Kaplan-Meier survival curve.
Time frame: From study entry to the first documented evidence of disease progression, assessed up to 5 years
Overall survival
Overall survival for each cohort will be summarized using a Kaplan-Meier survival curve.
Time frame: From study entry until death due to any cause, assessed up to 5 years
Quality of life assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core Cancer Module (QLQ-C30) and EORTC Brain Cancer Module (BCM-20)
Changes from baseline will be summarized for the total score and subscale scores. Responses will be scored and reported according to published methods. The baseline and change scores will be characterized descriptively.
Time frame: Baseline
Quality of life assessed using the EORTC QLQ-C30 and EORTC BCM-20
Changes from baseline will be summarized for the total score and subscale scores. Responses will be scored and reported according to published methods. The baseline and change scores will be characterized descriptively.
Time frame: Week 8
Cause of death classified as being due to systemic disease progression, primarily due to CNS disease progression, primarily due to treatment-related toxicity, or unrelated to the subject's breast cancer diagnosis
The proportion of patients who fall into each category will be tabulated.
Time frame: Up to 5 years
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