Safety Study of Combined Immunotherapy With Trastuzumab and Cetuximab in Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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One important approach to change the natural history of advanced breast cancer is that of designing new combination chemotherapies in which the best drugs already available are used together with new anticancer agents devoid of clinical cross-resistance. The possibility of exploiting the combined use of cetuximab and trastuzumab represents an option of potential great impact on the probability of response and long-term therapeutic results for patients with advanced breast cancer and HER2 overexpression.Therefore, patients with tumors that demonstrate EGFR expression and clear-cut erbB-2 overexpression (3+) or limited erbB-2 overexpression (+ or 2+) will be included in the study. Patients will be treated with trastuzumab and cetuximab to study the pharmacokinetics and potential drug/drug interaction of both antibodies as well as the safety and tolerability of this novel combination treatment.

Official Title
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Phase I Study Investigating the Combined Immunotherapy With Trastuzumab and Cetuximab in Patients With Metastatic Breast Cancer With High and Moderate HER2 Expression

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of metastatic breast cancer presence of at least 1 measurable lesion according to modified RECIST criteria Evidence (fluorescence in situ hybridization FISH) of Her-2 overexpression in tumor tissue:Group A: Her-2 +++, Group B: Her-2 + or ++ EGFR-expressing disease as assessed by immunohistochemistry Recovered from relevant toxicities from other treatment prior to study entry Exclusion Criteria: Prior treatment with trastuzumab for metastatic breast cancer (adjuvant therapy is allowed) Prior treatment with cetuximab Concomitant cytotoxic chemotherapy Treatment with any investigational agent(s) within 4 weeks prior to study entry Known allergic/hypersensitivity reaction to any of the components of study treatments severe dyspnea Myocardial infarction within 6 months prior to study entry, uncontrolled congestive heart failure; or any current grade 3 or 4 cardio-vascular disorder despite treatment History of significant neurologic or psychiatric disorders

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cetuximab|weekly i.v.|
|Drug: Trastuzumab|weekly i.v.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and drug/drug interaction of cetuximab and |  | repeated PK measurements week 1-13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the combination treatment |  | week 1 -13 | 
| Response |  | week 9 and 13 |