Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Everolimus; Trastuzumab; Paclitaxel
Intervention description: Everolimus (RAD001) was supplied as tablets in 3 different dosage strengths, 2.5, 5, and 10 mg. The drug was packaged in blisters containing 10 tablets per blister. Blisters and packaging labels were compliant with local regulations and were printed in local language.; Commercially-available trastuzumab was used in this study. A 4 mg/kg loading dose was administered, intra-venous (IV), over 90 minutes on Day 1 (if patient was not already receiving trastuzumab); this was followed by weekly trastuzumab 2 mg/kg IV administered over 30 minutes. For patients who continued to receive trastuzumab and everolimus after completion/discontinuation of chemotherapy in the core treatment phase, trastuzumab may have been administered once every 3 weeks at a dose of 6 mg/kg. PT = Paclitaxel & Trastuzumab; Commercially-available paclitaxel was used in this study. Paclitaxel infusion was administered on Days 1, 8, and 15 of each 28-day cycle, after administration of trastuzumab. Paclitaxel (80 mg/m2) was administered as a 60-minute continuous IV infusion after standard premedication. Patients received paclitaxel for 6 cycles. At the investigator's discretion, treatment with paclitaxel could continue beyond 6 cycles.
Intervention MeSH terms: Paclitaxel; Trastuzumab; Everolimus
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 88.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Cancer of the breast; Human mammary carcinoma; HER-2; Metastatic; everolimus; trastuzumab; paclitaxel

Summary:

      Phase I: will look at different dose levels and regimens of everolimus combined with weekly
      trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast
      cancer.

      Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined
      with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing
      metastatic breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female or male patients ≥ 18 years old with WHO performance status ≤ 1

          -  HER-2 over-expressing metastatic breast cancer cells confirmed by histology

          -  Progressive disease on prior trastuzumab alone/or in combination with other anticancer
             agents, or relapsed any time after completion of this therapy (phase l)

          -  Patient resistance to trastuzumab and taxanes (Phase ll)

          -  Measurable disease according to RECIST (Phase ll)

          -  Patients neurologically stable with adequate bone marrow, liver and renal function

        Exclusion Criteria:

          -  Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study
             treatment start

          -  Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have
             received these ≤ 4 weeks prior to study treatment start or patients who have received
             lapatinib ≤ 2 weeks prior to study treatment start

          -  Patients who have previously received mTOR inhibitors

        Other protocol-defined inclusion/exclusion criteria may apply