A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: trastuzumab-MCC-DM1
Intervention description: Intravenous escalating dose
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Healthy volunteers: No
Keywords: HER2-positive breast cancer; MBC; Trastuzumab emtansine; Herceptin; T-DM1

Summary:

      This is a phase I, multicenter, open-label, dose-escalation study of single-agent
      trastuzumab-MCC-DM1 administered by intravenous (IV) infusion in patients with HER2-positive
      metastatic breast cancer (MBC) who have previously received trastuzumab. The study will
      assess the safety, tolerability, and pharmacokinetics of trastuzumab-MCC-DM1 and determine
      the dose and schedule to be used in Phase II.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically documented, incurable, locally advanced or metastatic breast cancer

          -  Evaluable or measurable HER2-positive disease

          -  History of progression during or within 60 days after treatment with any prior
             trastuzumab-containing chemotherapy regimen for HER2-positive breast cancer

          -  Previous treatment with chemotherapy for MBC

          -  Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL

          -  Serum bilirubin ≤ 1.5 mg/dL; AST, ALT, and alkaline phosphatase ≤ 2.5 × upper limit of
             normal (ULN) except for: Patients with hepatic metastases: ALT and AST ≤ 5 × ULN
             Patients with hepatic and/or bone metastases: alkaline phosphatase ≤ 5 × ULN

          -  Serum creatinine ≤ 1.5 mg/dL or creatinine clearance of ≥ 60 mL/min based on a 24-hour
             urine collection

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

          -  Women of childbearing potential and men must agree to use an effective method of birth
             control (e.g., hormonal, barrier) while receiving study treatment

        Exclusion Criteria:

          -  History of significant cardiac disease, unstable angina, CHF, myocardial infarction,
             or ventricular arrhythmia requiring medication

          -  History of Grade ≥ 3 hypersensitivity reaction to trastuzumab

          -  History of any toxicity to trastuzumab that resulted in trastuzumab being permanently
             discontinued

          -  Symptomatic brain metastases or any radiation or surgery for brain metastases within 3
             months of first study treatment

          -  Require supplemental oxygen for daily activities

          -  Grade ≥ 2 peripheral neuropathy

          -  Bisphosphonate therapy for symptomatic hypercalcemia

          -  Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy
             for the treatment of breast cancer within 4 weeks of first study treatment

          -  Any experimental therapy within 4 weeks of first study treatment

          -  Any major surgical procedure within 4 weeks of first study treatment

          -  History of clinically symptomatic liver disease, including viral or other hepatitis,
             current or history of alcoholism, or cirrhosis

          -  Pregnancy or lactation

          -  Cardiac troponin I ≥ 0.2 ng/mL

          -  Ejection fraction < 50% or below the lower limit of normal determined by
             echocardiogram or MUGA scan

          -  Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent