A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

Genentech

Status and phase

Completed

Phase 1

Conditions

Metastatic Breast Cancer

Treatments

Drug: trastuzumab-MCC-DM1

Study type

Interventional

Funder types

Industry

Identifiers

NCT00932373

TDM3569g

Details and patient eligibility

About

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.

Enrollment

54 patients

Sex

All

Volunteers

No Healthy Volunteers

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