Efficacy Study of Single Agent Trastuzumab or Lapatinib to Treat HER2-Overexpressing Breast Cancer

A Phase II, Randomized Trial With Single Agent Trastuzumab or Lapatinib in Patients With Metastatic HER2-Overexpressing Breast Cancer

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

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).