GW572016 Combined With Trastuzumab For The Treatment Of Previously Trastuzumab-Treated Breast Cancer

Study Overview
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Brief Summary
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This is two-part study (Phase I/Phase II). Part I is designed to find the optimal (best) doses of GW572016 and trastuzumab when given together,Part II is designed to evaluate the tumor response rate (shrinkage or lack of growth) in patients receiving lapatinib and trastuzumab.

Official Title
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Phase I Study of Lapatinib in Combination With Trastuzumab

Conditions
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Neoplasms, Breast

Intervention / Treatment
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* Drug: GW572016 oral tablets


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with confirmed breast cancer who have received prior trastuzumab. Patients must have adequate blood, liver, and kidney function and either be fully active or restricted only in performing strenuous activity. Female patients of child-bearing potential must be willing to abstain from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication or be willing to consistently and correctly use an acceptable method of birth control. Exclusion criteria: Patients with certain heart problems.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW572016 in combination with trastuzumab<br>Lapatinib: A specified dose of lapatinib will be orally taken once daily, at least one hour before or one hour after the morning meal. Lapatinib should be taken at the same time of day wherever possible. The starting dose of lapatinib should be 750 mg/day, which will be increased to 1000 mg/day (dose escalation group) according to the dose escalation criteria. Trastuzumab: Trastuzumab (4 mg/kg/day in the first week and 2 mg/kg/day for the 2nd and subsequent weeks) will be administered by intravenous infusion over at least 90 minutes immediately after administration of lapatinib. The fifth (Day 36) and subsequent doses may be administered up to 3 days after the scheduled date. In this case, however, the all following doses should be administered at one-week intervals. | Drug: GW572016 oral tablets<br>* Tablets contain 405mg of lapatinib ditosylate monohydrate, equivalent to 250mg lapatinib free base per tablet. Oval, orange, film-coated tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal doses and toleration of the two drugs administered together Tumor progression measured by radiological imaging 4-8 weekly | To confirm the safety and tolerability of the recommended dose of lapatinib in combination with trastuzumab which was determined in a preceding overseas study, and to determine the recommended dose in Japan. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit Time to tumor response Length of response Time to progression of cancer 6 month progression free survival Overall survival as well as specific biomarkers in tumor tissue |  | 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ErbB2, Stage IV breast cancer, ErbB1, breast cancer, lapatinib, Herceptin, trastuzumab