Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Everolimus; Placebo; Trastuzumab; Paclitaxel
Intervention description: Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).; Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).; Trastuzumab, 2 mg/kg weekly was used intravenously.; Paclitaxel, 80 mg/m2 weekly was used intravenously.
Intervention MeSH terms: Paclitaxel; Trastuzumab; Everolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 719.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; HER2+; mTOR; everolimus; RAD001; first line; metastatic; locally advanced; Trastuzumab; Paclitaxel; First Line Therapy; HER2 Positive; Metastatic Breast Cancer

Summary:

      The purpose of this Phase III study was to confirm the value of adding everolimus to weekly
      paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult Women (≥ 18 years old).

          -  Histologically or cytologically confirmed invasive breast carcinoma with local
             recurrence or radiological evidence of metastatic disease.

          -  Must have at least one lesion that can be accurately measured or bone lesions in the
             absence of measurable disease.

          -  HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization
             positive).

          -  Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant
             treatment is allowed but should be discontinued > 12 months prior to randomization.

          -  Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic
             settings) is allowed but should be discontinued at randomization. Patients treated
             with bisphosphonates at entry or who start bisphosphonates during study may continue
             this therapy during protocol treatment.

          -  Documentation of negative pregnancy test.

          -  Organ functions at time of inclusion.

        Exclusion Criteria:

          -  Prior mTOR inhibitors for the treatment of cancer.

          -  Other anticancer therapy for locally advanced or metastatic breast cancer except for
             prior hormonal therapy.

          -  Patients with only non-measurable lesions other than bone metastasis (e.g. pleural
             effusion, ascites, etc).

          -  Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization

          -  History of central nervous system metastasis.

          -  Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the
             upper gastrointestinal tract.

          -  Serious peripheral neuropathy.

          -  Cardiac disease or dysfunction.

          -  Uncontrolled hypertension.

          -  HIV.

          -  Pregnant,