A Study Of Everolimus, Trastuzumab And Vinorelbine In HER2-Positive Breast Cancer Brain Metastases
Purpose: This study is a single-arm, open-label phase II clinical trial testing the hypothesis that daily everolimus plus weekly vinorelbine and trastuzumab will be effective, safe, and tolerable among patients with HER2-positive breast cancer brain metastases. Once enrolled, patients will receive everolimus PO daily in combination with weekly intravenous (IV) vinorelbine and trastuzumab. Cycles will be repeated every 3 weeks (21 days). At the time of progression, patients will come off study.
Participants: Up to 35 adults over 21 with HER-2 positive breast cancer that has metastasized to the brain.
HER-2 Positive Breast Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Evaluating The Efficacy And Tolerability Of Everolimus (RAD001) In Combination With Trastuzumab And Vinorelbine In The Treatment Of Progressive HER2-Positive Breast Cancer Brain Metastases|
- intracranial response rate- modified RECIST Criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]response will be evaluated via gadolinium-enhanced brain MRI using modified RECIST criteria for all evaluable patients. A responder will be a patient whose best overall response is a CR or PR
- Intracranial Response Rate- MacDonald Criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]intracranial response rate will be evaluated via gadolinium-enhanced MRI using MacDonald criteria
- Extracranial response [ Time Frame: 3 years ] [ Designated as safety issue: No ]Extracranial response will be measured using RECIST 1.1 criteria.
- Toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]Toxicity will be assessed according to the NCI CTCAE v4.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Everolimus with Vinorelbine and trastuzumab
daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab
everolimus 5 mg PO daily as two 2.5-mg tablets
Other Name: RAD001Drug: Vinorelbine
vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.
Other Name: NavelbineDrug: Trastuzumab
2 mg/kg IV administered over 30 minutes weekly
Other Name: Herceptin
STUDY OBJECTIVES Primary Objective -To determine the intracranial objective response rate of mTOR inhibition (everolimus) in combination with vinorelbine and trastuzumab in the treatment of HER2-positive, progressive breast cancer brain metastases as defined via modified RECIST criteria.
- To determine the intracranial objective response rate of mTOR inhibition (everolimus) in combination with vinorelbine and trastuzumab in the treatment of HER2-positive, progressive breast cancer brain metastases as defined by MacDonald criteria.
- To evaluate the safety and tolerability of everolimus in combination with trastuzumab and vinorelbine as assessed via the NCI CTCAE version 4.0
- To evaluate time to intracranial progression after administration of everolimus in combination with trastuzumab and vinorelbine as defined via modified RECIST criteria
- To evaluate the extracranial objective response rate as determined by RECIST 1.1 criteria after administration of everolimus in combination with trastuzumab and vinorelbine.
- To evaluate the extracranial time to progression as determined by RECIST 1.1 criteria after administration of everolimus in combination with trastuzumab and vinorelbine.
- To evaluate progression free survival (PFS) and overall survival (OS) after administration of everolimus in combination with trastuzumab and vinorelbine.
- To evaluate the impact of everolimus in combination with trastuzumab and vinorelbine on quality of life as measured by the FACT-B and FACT-Br questionnaires.
-To evaluate biomarkers in archival tumor tissue samples and correlate with therapeutic response to everolimus in combination with vinorelbine and trastuzumab.
Following Hepatitis B antiviral prophylaxis if required, or following screening and informed consent if antiviral therapy is not needed, treatment will be initiated with everolimus PO daily in combination with weekly intravenous (IV) vinorelbine and trastuzumab (Days 1, 8, and 15)
A cycle is defined as 3 weeks (21 days). Cycles of therapy will be repeated until documented disease progression, unacceptable toxicity, or patient withdrawal from study for other reasons, including death.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01305941
|Contact: Donna Rowe, RN||(919) email@example.com|
|United States, Alabama|
|University Of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator: Lisle Nabell, MD|
|United States, Florida|
|MD Anderson Cancer Center- Orlando||Withdrawn|
|Orlando, Florida, United States, 32806|
|United States, Illinois|
|University Of Chicago Medical Center||Withdrawn|
|Chicago, Illinois, United States, 60637|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Rachel Phipps, RN|
|Principal Investigator: Carey K Anders, MD|
|Carolinas Healthcare System||Active, not recruiting|
|Charlotte, North Carolina, United States, 28203|
|Kinston Medical Specialists, PA||Withdrawn|
|Kinston, North Carolina, United States, 28501|
|Marion L. Shepard Cancer Center||Withdrawn|
|Washington, North Carolina, United States, 27889|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37212|
|Principal Investigator: Vandana Abramson, MD|
|United States, Virginia|
|University of Virginia||Withdrawn|
|Charlottesville, Virginia, United States, 22903|
|Principal Investigator:||Carey K Anders, MD||UNC Lineberger Comprehensive Cancer Center|