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

Study Overview
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Brief Summary
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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

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

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab or Lapatinib


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 - Trastuzumab<br>Day1 Week1: 8 mg/kg iv in 90 min. Following 1st week: 2 mg/kg once/weekly for 8 weeks | Drug: Trastuzumab or Lapatinib<br>* Trastuzumab: loading dose 8 mg/kg iv in 90 min.followed by weekly doses of 2 mg/kg Lapatinib: 1500 mg/die orally<br>|
| Experimental: 2 - Lapatinib<br>1500 mg/die orally | Drug: Trastuzumab or Lapatinib<br>* Trastuzumab: loading dose 8 mg/kg iv in 90 min.followed by weekly doses of 2 mg/kg Lapatinib: 1500 mg/die orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of clinically definite response confirmed by CT or MRI |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) and duration of response in patients treated with Trastuzumab |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, HER2, Trastuzumab, Lapatinib, HER2 gene-amplification