Metastatic Breast Cancer
Conditions
Keywords
breast cancer, HER2, Trastuzumab, Lapatinib, HER2 gene-amplification
Brief summary
This study will evaluate the activity of single agent trastuzumab or lapatinib in patients not previously treated for HER-2 positive (FISH positive) metastatic breast cancer. A companion biological study will assess factors correlated with sensitivity or resistance to either one of the compounds
Interventions
Trastuzumab: loading dose 8 mg/kg iv in 90 min.followed by weekly doses of 2 mg/kg Lapatinib: 1500 mg/die orally
Sponsors
Azienda Ospedaliera Ordine Mauriziano di Torino
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Women aged 18-75 years * Histologically or cytologically confirmed metastatic disease. * HER2-Overexpression proven by Fluorescence in Situ Hybridization (FISH). * Availability of paraffin-embedded block of either primitive tumor and/or biopsy of metastases. * No prior chemotherapy for metastatic or locally advanced disease. Patients with hormone receptor (oestrogen and/or progesterone) positive breast cancer can be eligible provided that they had received only ONE line of hormonal therapy for metastatic disease. * For patients undergoing hormonal therapy for metastatic disease, disease progression must be confirmed according to RECIST criteria. * At least 20% increase in the sum of longest diameters, OR * Evidence of new metastatic lesions or progression of pre-existing non-target lesions. * Presence of at least one monodimensionally measurable lesion. Patients without clinically or radiologically proven evidence of disease are not eligible. * Patients with exclusively skin disease are eligible, provided that the disease evolution under treatment can be photographically documented. * Patients with involvement of NCS, besides presence of measurable lesions, are eligible provided that: * Brain lesion/s has/have been radically resected; * Brain lesion/s has/have obtained complete remission following radiation therapy. Complete remission must be documented by TC or RMN. * At least 4-week interval from end of radiotherapy, hormono- or immunotherapy and enrollment in this study. * ECOG PS \</= 2 and life expectancy of at least 6 months. * Liver metastases involving \< 30% of liver volume. * Adequate hematopoietic, liver and renal function * Written informed consent. * Patients with childbearing potential must have negative pregnancy test and must use adequate contraceptive measures during treatment. * Prior treatment with Trastuzumab as adjuvant therapy is permitted provided that it was completed at least 12 months prior enrollment in this study.
Exclusion criteria
* Prior chemotherapy for metastatic disease. * Active pregnancy or breastfeeding. * Previous treatment with Lapatinib. * Previous therapy with mono- or policlonal antibodies for metastatic disease. * Patients with bone involvement or pleural effusion/ascites as unique localization of disease. * Patients with dyspnea due to presence of disease (lymphangitis) or requiring oxygen therapy. * Patients with clinically evident hearth disease and/or active infectious diseases. * Patients with not resected or not irradiated brain and/or leptomeningeal metastases. * Prior or actual concurrent neoplasms, with the exception of adequately treated carcinoma della cervice uterina and basal cell or squamocellular carcinoma of the skin. * Patients with uncontrolled serious illnesses that may compromise the compliance of the patient to the treatment. * Previous allergic reactions towards any excipient in the composition of Trastuzumab or Lapatinib. * Use of any experimental drug within 4 weeks prior initiation of study treatment. * Women with childbearing potential who refuse to use adequate contraceptive measures. * Patients unable to give written informed consent or are not compliant with treatment. * Patients with great tumor involvement (\> 30% dof hepatic volume, etc).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evidence of clinically definite response confirmed by CT or MRI | 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Time to Progression (TTP) and duration of response in patients treated with Trastuzumab | 8 weeks |
Countries
Italy
Contacts
Primary ContactFilippo Montemurro, MD
Backup ContactManuela Muliello, Study Coordinator
Outcome results
None listed