Sorafenib in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well sorafenib works in treating patients with metastatic breast cancer. Sorafenib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor.

Detailed Description
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OBJECTIVES: I. Determine the tumor response rate in patients with metastatic breast cancer previously treated with an anthracycline- and/or taxane-containing regimen receiving sorafenib. II. Assess the toxicity profile of this drug in these patients. III. Determine time to disease progression and survival time of patients treated with this drug. IV. Correlate pre-treatment levels of activated ERK1/2 with tumor response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months until disease progression and then every 3 months for up to 5 years.

Official Title
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Phase II Trial of Raf Kinase Inhibitor BAY 43-9006 as Single Oral Agent in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane

Conditions
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Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
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* Drug: sorafenib tosylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed breast cancer Clinical evidence of metastatic disease Measurable disease HER2-positive or -negative disease If HER2 gene amplified or strongly positive for HER2 by immunohistochemistry, patient must have had prior treatment containing trastuzumab (Herceptin®) unless contraindicated Previously treated with anthracycline- and/or taxane-containing regimen in the neoadjuvant, adjuvant, or metastatic setting Candidate for first- or second-line chemotherapy for metastatic disease Core block or tumor slides of the primary or metastatic tumor available No known brain metastases Hormone receptor status: Not specified Male or female Performance status - ECOG 0-1 At least 3 months WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.5 g/dL No evidence of bleeding diathesis Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 3 times ULN Alkaline phosphatase ≤ 3 times ULN PT normal PTT normal INR normal Creatinine ≤ 1.5 times ULN Calcium normal No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension No gastrointestinal tract disease that would preclude taking oral medication No active peptic ulcer disease Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other study agents No ongoing or active infection No psychiatric illness or social situation that would preclude study participation No other uncontrolled illness See Disease Characteristics More than 4 weeks since prior immunotherapy No concurrent anticancer immunotherapy No concurrent bevacizumab See Disease Characteristics More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No more than 1 prior chemotherapy regimen for metastatic disease No concurrent anticancer chemotherapy Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting is allowed No concurrent anticancer hormonal therapy No prior radiotherapy to ≥ 25% of the bone marrow More than 4 weeks since prior radiotherapy More than 4 weeks since prior major surgery No prior surgical procedure that would affect gastrointestinal absorption No other concurrent drugs that target vascular endothelial growth factor (VEGF) or VEGF receptors No concurrent antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer therapy No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following: Phenytoin Carbamazepine Phenobarbital No concurrent rifampin No concurrent Hypericum perforatum (St. John's wort) No concurrent therapeutic anticoagulation Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial devices is allowed

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: sorafenib tosylate<br>* Given orally<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of confirmed tumor responses, graded according to RECIST criteria | A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The tumor response rate is defined as the total number of eligible patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of eligible patients enrolled on study. A 90% confidence interval for the true response rate will be constructed using the Duffy-Santner approach. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Estimated using the Kaplan-Meier method. | Time from registration to disease progression, assessed up to 5 years | 
| Survival time | Estimated using the Kaplan-Meier method. | Time from registration to death, assessed up to 5 years | 
| Incidence of adverse events, graded according to the NCI-CTC version 3 | The maximum grade for each type of toxicity will be recorded for each patient at each treatment evaluation. The frequency of each type of toxicity will be determined. | Up to 5 years |