Phase 1
N=52
A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen
Metastatic Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00932373 ↗Enrolled (actual)
52
Serious AEs
34.6%
Results posted
Jul 2015
Primary outcome: Primary: Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment — 100; 100; 100; 100 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- trastuzumab-MCC-DM1 (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Genentech, Inc.
- Primary completion
- Jun 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment |
100; 100; 100; 100; 100; 100 | — |
| PRIMARY Number of Patients With Dose Limiting Toxicities (DLTs) |
0; 0; 0; 0; 0; 2 | — |
| PRIMARY Maximum Tolerated Dose (MTD) |
3.6; 2.4 | — |
| PRIMARY Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations |
9.63; 13.3; 20.3; 76.3; 76.2; 130 | — |
| PRIMARY PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations |
14.5; 24.5; 42.9; 330; 300; 673 | — |
| PRIMARY PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations |
1.3; 1.3; 1.3; 2.2; 3.1; 4.1 | — |
| SECONDARY Percentage of Participants With an Objective Response |
0; 0; 0; 100; 26.7; 0 | — |
| SECONDARY Duration of Objective Response |
NA; 10.5; NA; 2.9; NA; 5.6 | — |
| SECONDARY Progression-free Survival |
2.7; 1.7; NA; NA; 10.4; NA | — |
| SECONDARY Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine |
0.0; 3.7; 4.3; 0.0 | — |
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 360 mg/m2 or equivalent
Data sourced from ClinicalTrials.gov (NCT00932373). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.