Tipifarnib Plus Trastuzumab in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining tipifarnib with trastuzumab may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining tipifarnib with trastuzumab in treating patients who have metastatic breast cancer.

Detailed Description
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OBJECTIVES: Determine the antitumor activity of tipifarnib and trastuzumab (Herceptin) in patients with metastatic breast cancer. Determine the safety and tolerability of this regimen in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive oral tipifarnib twice daily on days 1-21 and trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 18-40 patients will be accrued for this study within 9-20 months.

Official Title
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A Phase II Evaluation Of The Efficacy And Safety Of R115777 (NSC702818) A Non-Peptidomimetic Farnesyl Transferase Inhibitor, And Trastuzumab In Patients With Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Drug: tipifarnib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic adenocarcinoma of the breast HER2/neu 3+ by immunohistochemical staining 2+ eligible provided HER2/neu positive by fluorescent in-situ hybridization (FISH) HER2/neu positive by FISH alone allowed Unidimensionally measurable disease At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Must have received prior trastuzumab (Herceptin) Patients with known brain metastases meeting any of the following criteria are not eligible: Require high-dose steroid therapy or enzyme-inducing anticonvulsant drugs No prior cranial radiotherapy Have progressive neurologic dysfunction that would preclude study evaluation Have evidence of progressive CNS disease by CT scan or MRI Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age Over 18 Sex Male or female Menopausal status Not specified Performance status ECOG 0-2 OR Karnofsky 70-100% Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.0 g/dL Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN (5 times ULN if liver metastases present) Renal Creatinine no greater than 1.5 times ULN OR Creatinine clearance greater than 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Ejection fraction greater than 50% by MUGA or echocardiogram Gastrointestinal No gastrointestinal tract disease resulting in an inability to tolerate oral medication No requirement for IV alimentation No active peptic ulcer disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No significant traumatic injury within the past 21 days No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No ongoing or active infection No prior allergic reaction attributed to compounds of similar chemical or biological composition to tipifarnib (e.g., quinolones) or trastuzumab No psychiatric illness or social situation that would preclude study compliance No other concurrent medical illness that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No prior bone marrow transplantation with high-dose chemotherapy No concurrent immunotherapy Chemotherapy See Biologic therapy No more than 2 prior chemotherapy regimens for metastatic disease More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior combination chemotherapy allowed No concurrent chemotherapy Endocrine therapy See Disease Characteristics Prior hormonal therapy allowed No concurrent hormonal therapy for cancer Radiotherapy See Disease Characteristics More than 4 weeks since prior wide-field radiotherapy and recovered No concurrent radiotherapy Surgery Prior modified radical mastectomy or lumpectomy with axillary node dissection allowed Prior resection of metastatic lesions allowed More than 21 days since prior major surgery No prior surgery affecting absorption Other No prior tipifarnib More than 6 weeks since initiation of bisphosphonate therapy (if bone lesions are the only site of measurable disease) Bisphosphonate therapy may not be initiated during study No other concurrent investigational agents No other concurrent anticancer therapy No concurrent antacids within 2 hours of study drug

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: trastuzumab|nan|
|Drug: tipifarnib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 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, male breast cancer