Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Combining trastuzumab with erlotinib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with erlotinib as first-line therapy in treating women who have metastatic breast cancer associated with HER2/neu overexpression.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and recommended phase II dose of erlotinib when combined with trastuzumab (Herceptin) as first-line therapy in women with metastatic breast cancer associated with HER2/neu overexpression. (Phase I closed to accrual as of 01/2004) Determine the safety profile of this regimen in these patients. Determine the rate and duration of objective response in patients treated with this regimen. Determine the pharmacologic behavior of this regimen in these patients. Determine time to disease progression and duration of survival in patients treated with this regimen. Correlate the antitumor activity of this regimen with epidermal growth factor receptor expression in these patients. OUTLINE: This is a dose-escalation study of erlotinib. (Phase I closed to accrual as of 01/2004). Patients receive oral erlotinib once daily beginning on day 2 and trastuzumab (Herceptin) IV over 30-90 minutes (1-4 hours after erlotinib) once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for the phase I portion (closed to accrual as of 01/2004) and 27-81 patients will be accrued for the phase II portion of this study.

Official Title
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Phase I/II Study Of Herceptin Combined With OSI-774 In The First-Line Treatment Of Metastatic Breast Cancer Associated With HER2/Neu Overexpression

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged > 18 years Histologically documents metastatic breast cancer HER2 positive using Fluorescence In Situ Hybridization (FISH) For phase I, patients who have previously received treatment for their metastatic disease are allowed to participate. For the phase II portion of the study, patients must have measureable disease (> 2 cm; > 1 cm on spiral CT scan) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 A life expectancy of > 3 months Use of effective means of contraception Exclusion Criteria: For Phase II, prior cytotoxic chemotherapy and/or prior Herceptin for their metastatic disease. Prior treatment in the adjuvant setting is allowed.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>please see intervention description | Biological: trastuzumab<br>* Day 1 4mg/kg IV 2 mg/kg IV weekly.<br>* Other names: Herceptin;Drug: erlotinib hydrochloride<br>* 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.<br>* Other names: OSI-774;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart. | Complete Response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission. Partial Response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission. | 5 years | 
| Recommended Dose for Phase II |  | treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Objective Response |  | 5 years | 
| Incidence of Adverse Events |  | 5 years | 
| Serum Concentration of Herceptin at Specified Time-points. |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer