Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer
Condition: HER2/Neu Over-expressing Locally Advanced Breast Cancer; Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: everolimus; Placebo; vinorelbine; trastuzumab
Intervention description: Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.; Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.; intravenous vinorelbine (25 mg/m2 weekly); intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
Intervention MeSH terms: Trastuzumab; Everolimus; Vinorelbine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 569.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic breast cancer; locally advanced breast cancer; HER2/neu positive breast cancer; HER2/neu over-expressing; progressive-free survival (PFS); over survival (OS); bolero; bolero 3; Breast cancer; everolimus; HER+; vinorelbine; herceptin; trastuzumab; RAD001

Summary:

      This phase III, double-blind, placebo-controlled multinational study will assess the
      combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine
      and trastuzumab with respect to progressive-free survival and over survival in HER2/neu
      positive women with locally advanced or metastatic breast cancer who are resistant to
      trastuzumab and have been pre-treated with a taxane.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed invasive breast carcinoma with locally
             recurrent or radiological evidence of metastatic disease. Locally recurrent disease
             must not be amenable to resection with curative intent.

          -  HER2+ status defined as IHC 3+ staining or in situ hybridization positive

          -  Patients with resistance to trastuzumab

          -  Prior taxane therapy

          -  Patients with an ECOG performance status of 0 - 2

          -  Patients with measurable disease as per RECIST criteria

          -  Documentation of negative pregnancy test for patients of child bearing potential prior
             to enrollment within 7 days prior to randomization. Sexually active pre-menopausal
             women must use adequate contraceptive measures, excluding estrogen containing
             contraceptives, while on study;

          -  Patients must meet laboratory criteria defined in the study within 21 days prior to
             randomization

        Exclusion Criteria:

          -  Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer

          -  More than three prior chemotherapy lines for advanced disease.

          -  Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated
             asymptomatic CNS metastases are allowed provided that the last treatment for CNS
             metastases was completed >8 weeks prior to randomization

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of oral everolimus

          -  Peripheral neuropathy ≥ grade 2 at randomization

          -  Active cardiac disease

          -  History of cardiac dysfunction

          -  Any malignancy within 5 years prior to randomization, with the exception of adequately
             treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or
             non-melanomatous skin cancer

          -  Known hypersensitivity to any study medication

          -  Breastfeeding or pregnant