Breast Cancer, Neoplasm Metastasis
Conditions
Keywords
Breast cancer, metastatic, cardiotoxicity, liposomal, doxorubicin, trastuzumab, docetaxel, HER2/neu positive metastatic breast cancer
Brief summary
This is an open phase II study evaluating the efficacy and safety of the non pegylated liposomal doxorubicin (Myocet®), trastuzumab (Herceptin®), and docetaxel (Taxotere®) combination as first-line treatment of patients with metastatic HER2/neu positive breast cancer.
Detailed description
Phase II non comparative study, assessing the safety (primarily cardiac safety) and efficacy in patients with locally advanced or metastatic HER2/neu positive breast cancer not yet treated with chemotherapy for metastatic disease. Myocet and Taxotere will be given for a maximum of 6 cycles, Herceptin treatment for 1 year is recommended. Endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.
Interventions
DRUGNon pegylated liposomal doxorubicin, trastuzumab, docetaxel
max. 6 courses
Sponsors
Cephalon
Sanofi
Laurence J.C. van Warmerdam
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with histologically documented metastatic or locally advanced metastatic HER2/neu positive breast cancer at 1st line of palliative chemotherapy. * In the case of previous adjuvant or neoadjuvant chemotherapy with anthracyclines or taxanes, this must have been completed more than 12 months before inclusion. * In the case of previous adjuvant or neoadjuvant chemotherapy, cumulative anthracycline dose ≤ 240 mg/m2 of doxorubicin or 450 mg/m2 of epirubicin or 75 mg/m2 of mitoxantrone on inclusion. * Previous endocrine therapy is authorized (endocrine therapy other than goserelin must be stopped before starting treatment). * Previous radiotherapy is authorized, if discontinued ≥ 4 weeks prior to inclusion in the study and if \< 10% of the bone marrow was within the irradiated area. * Age ≥ 18 years. * Performance status 0,1, or 2. * Life expectancy ≥ 3 months. * Evaluable disease. * Normal LVEF (multigated acquisition \[MUGA\] scan or echocardiography). * Normal haematological, hepatic and renal parameters: neutrophils ≥ 1.5 x 10\^9/l; platelets ≥ 100 x 10\^9/l; hemoglobin (Hb) ≥ 6 mmol/L; total bilirubin ≤ 1.5 times the upper limit of normal (ULN); transaminases ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 x ULN; creatinine ≤ 1.5 x ULN. * Dated and signed written informed consent.
Exclusion criteria
* Previous chemotherapy for metastatic disease. * History of other cancer, except for cervical carcinoma in situ treated by cone resection or basal cell or squamous cell skin cancer. * History of congestive heart failure or myocardial infarction ≤ 1 year; cardiac function: NYHA ≥ 2 or LVEF \< 50%. * Uncontrolled significant heart disease, such as unstable angina. * Poorly controlled hypertension. * Performance status 3, 4. * Symptomatic or progressive brain metastases. * Active infection or other serious underlying disease. * Concomitant participation in other clinical trials. * Pregnant women or nursing mothers; patients of childbearing potential without effective contraception. * Absolute medical contraindication to the use of corticosteroid premedication. * Allergy to polysorbate 80, doxorubicin, or egg lecithin. * NCI-CTC grade \> 1 peripheral neuropathy. * Patients not able to comply with regular medical follow-up
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Decline in LVEF of ≥ 10% to < 50% without signs or symptoms of CHF | treatment period |
| Cardiotoxicity (definite or probable cardiac death) | treatment period |
| Signs or symptoms of congestive heart failure (CHF), New York Heart Association (NYHA) class III-IV | treatment period |
| Decline in left ventricular ejection fraction (LVEF) of ≥ 5% to < 50% with mild signs or symptoms of CHF (NYHA class < III) | treatment period |
Secondary
| Measure | Time frame |
|---|---|
| Frequency and severity of intercurrent events according to the National Cancer Institute - Common Terminology Criteria (NCI-CTC) classification | treatment period |
| Response rate | treatment period |
| Median time to progression | treatment period |
| Progression free survival | treatment period |
Countries
Netherlands
Outcome results
None listed