Phase 1b/2 Trial Using Lapatinib, Everolimus and Capecitabine for Treatment of HER-2 Positive Breast Cancer With CNS Metastasis
This is a phase 1b/2 study to evaluate the safety and clinical activity of the combination of lapatinib, everolimus and capecitabine for the treatment of participants with HER2+ breast cancer with metastases in the brain who have progressed on trastuzumab.
The combination of 2 drugs able to reach the brain (lapatinib and everolimus) that target different parts of the HER2 signaling pathway plus chemotherapy (capecitabine) that has proven benefits in metastatic breast cancer may lead to improved clinical outcomes for participants with CNS metastasis.
Participants will undergo brain MRIs and CT scans of the chest and abdomen to evaluate response to the treatment, regular laboratory tests and echocardiogram or Multi Gated Acquisition Scan (MUGA) to assess cardiac activity
Central Nervous System Metastases
HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1b/2 Single-arm Trial Evaluating the Combination of Lapatinib, Everolimus and Capecitabine for the Treatment of Patients With HER2-positive Metastatic Breast Cancer With CNS Progression After Trastuzumab|
- CNS objective response rate defined as either a complete response or partial response provided there is no progression of extra-CNS disease, increasing steroid requirements, or worsening of NSS measured using RECIST v1.1 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Estimated with a 95% confidence interval. Chi-square test will be used evaluate if the CNS response rate at week 12 is significantly higher than 20%.
- Body system, severity and relation with study treatment of adverse events graded according to the National Institute of Health (NIH)/ National Cancer Institute (NCI) Common Toxicity Criteria (CTC) v4.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
- Progression-free survival (PFS) by the RECIST v1.1 [ Time Frame: Interval between the date of study enrollment and the earliest date of disease progression, assessed up to 1 year after end of treatment ] [ Designated as safety issue: No ]The distribution of PFS and OS will be estimated using Kaplan-Meier method and survival curves for PFS and OS will be plotted. Median PFS and median OS will be obtained.
- Overall survival (OS) [ Time Frame: Interval between the date of study enrollment and the date of death, assessed up to 12 months after end of treatment ] [ Designated as safety issue: No ]The distribution of PFS and OS will be estimated using Kaplan-Meier method and survival curves for PFS and OS will be plotted. Median PFS and median OS will be obtained.
- Extra CNS response according to RECIST1.1 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Will be analyzed similarly to CNS objective response rate.
|Study Start Date:||June 2013|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (lapatinib ditosylate, everolimus, capecitabine)
Patients receive lapatinib ditosylate PO QD and everolimus PO QD on days 1-21, and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
Drug: lapatinib ditosylate
Other Names:Drug: everolimus
Other Names:Drug: capecitabine
Other Names:Other: laboratory biomarker analysis
I. Central nervous system (CNS) objective response rate at 12 weeks: defined as either a complete response or partial response provided there is no progression of extra-CNS disease, increasing steroid requirements, or worsening of neurologic signs and symptoms (NSS)^34 Lesions will be measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
I. Safety and tolerability. II. Median progression free survival. III. Median overall survival. IV. CNS objective response rate and clinical benefit rate (complete response, partial response and stable disease lasting at least 6 months).
V. Extra-CNS objective response rate according to RECIST1.1.
Patients receive lapatinib ditosylate orally (PO) once daily (QD) and everolimus PO QD on days 1-21, and capecitabine PO twice daily (BID) on days 1-14. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment or treatment discontinuation, patients will complete 2 follow up visits within 7 days and at 30 days and then will be followed for survival every 3 months for up to 12 months.
|United States, California|
|Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Sara A. Hurvitz 888-798-0719 email@example.com|
|Principal Investigator: Sara A. Hurvitz|
|Principal Investigator:||Sara Hurvitz||Jonsson Comprehensive Cancer Center|