Clinical trial NCT01305941
Conditions: HER-2 Positive Breast Cancer
Keywords: everolimus trastuzumab vinorelbine RAD001 Breast Cancer Herceptin Navelbine Lineberger Comprehensive Cancer Center Brain Metastases
Sponsor: UNC Lineberger Comprehensive Cancer Center
Start date: 2011-09-01; Completion date: 2017-10-16
Enrollment: 32 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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 human epidermal growth factor receptor 2 (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.

Detailed description:
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.

Secondary Objectives

* To determine the intracranial objective response rate of mechanistic target of rapamycin (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 Functional Assessment of Cancer Therapy Breast (FACT-B) and Functional Assessment of Cancer Therapy Brain (FACT-Br) questionnaires.

Exploratory Objective

-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.

Arms: arm 1: daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab
Interventions: intervention 1: Everolimus intervention 2: Vinorelbine intervention 3: Trastuzumab
Intervention descriptions: intervention 1: everolimus 5 mg PO daily as two 2.5-mg tablets intervention 2: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly. intervention 3: 2 mg/kg IV administered over 30 minutes weekly

Protocol documents: