VEGF Trap 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 VEGF Trap works in treating patients with metastatic breast cancer. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the antitumor activity of VEGF Trap, in terms of tumor response rate, in patients with metastatic breast cancer who have received =< 2 prior chemotherapy regimens for metastatic disease, including a taxane and/or anthracycline. II. Assess the 6-month progression-free survival rate in patients treated with VEGF Trap. SECONDARY OBJECTIVES: I. Describe the adverse event profile (grade using the NCI CTCAE version 3.0) of VEGF Trap in these patients. II. Describe the progression-free survival times in patients treated with VEGF Trap. III. Describe the overall survival of patients treated with VEGF Trap. IV. Describe the duration of response in patients treated with VEGF Trap. OUTLINE: This is a multicenter study. Patients receive VEGF Trap IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

Official Title
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Phase II Trial of VEGF Trap in Patients With Metastatic Breast Cancer Previously Treated With Anthracycline and/or Taxane

Conditions
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Metastatic Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
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* Biological: ziv-aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the breast Clinical evidence of metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease Prior neoadjuvant or adjuvant chemotherapy allowed* At least 1 prior regimen (in any setting) must have included a taxane and/or an anthracycline Measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured per RECIST criteria No nonmeasurable disease, defined as all other lesions, including small lesions(longest diameter < 20 mm) and truly nonmeasurable lesions, including the following: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Patients with HER2-positive tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization [FISH]) must have received ≥ 1 prior trastuzumab (Herceptin®)-containing regimen in either the adjuvant or metastatic setting, unless there was a contraindication No known CNS metastases No evidence of leptomeningeal involvement Hormone receptor status not specified Male or female Menopausal status not specified ECOG performance status 0-1 Life expectancy > 3 months WBC ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ Hemoglobin > 8.0 g/dL Bilirubin ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN AST and ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study treatment No significant traumatic injury within the past 4 weeks No history of allergy or hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, drug product excipients, or agents chemically or biologically similar to VEGF Trap No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days No nonhealing wound, fracture, or ulcer No stage III or IV invasive, nonbreast malignancy within the past 5 years No history of lung carcinoma of squamous cell type No clinically significant cardiovascular disease, including any of the following: Cerebrovascular accident or stroke within the past 6 months Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg OR systolic BP > 180 mm Hg if diastolic blood pressure < 90 mm Hg on ≥ 2 separate occasions within the past 3 months Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months New York Heart Association class III or IV cardiovascular disease Serious cardiac arrhythmia requiring medication Peripheral vascular disease ≥ grade 2 within the past 6 months Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months No evidence of bleeding diathesis or uncontrolled coagulopathy No active, unresolved infection No serious concurrent medical condition that would preclude study participation No other condition or circumstance that would preclude compliance with study requirements See Disease Characteristics Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting allowed No prior bevacizumab More than 4 weeks since prior chemotherapy, endocrine therapy, experimental drug therapy, or immunotherapy and recovered More than 4 weeks since prior major surgery or open biopsy More than 7 days since prior core biopsy More than 2 weeks since prior radiotherapy, except if to a nontarget lesion only Prior radiotherapy to a target lesion allowed only if there has been clear progression of the lesion since radiotherapy was completed Prior single-dose palliative radiotherapy within the past 2 weeks allowed No concurrent major surgery No concurrent trastuzumab Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met: INR in-range (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent participation in another investigational clinical trial No other concurrent chemotherapeutic agents, endocrine therapy, biologic agents, radiotherapy, or other nonprotocol antitumor therapy

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: Treatment (ziv-afibercept)<br>Patients receive VEGF Trap IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Biological: ziv-aflibercept<br> <br> * Other names: Zaltrap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Confirmed Tumor Response | Confirmed tumor response was defined as the total number of efficacy-evaluable patients who achieved a complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on 2 consecutive evaluations at least 8 weeks apart. | Up to 5 years | 
| Proportion of Patients Receiving Vascular Endothelial Growth Factor (VEGF) Trap With 6-month Progression-free Survival | The 6-month progression free survival rate was defined as the proportion of efficacy-evaluable patients on study treatment and progression-free 6 months from registration. Patients who died without documentation of progression will be considered to have progressed on the date of their death. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who died without documentation of progression being considered to have progressed on the date of their death. | Time from registration to disease progression or death (up to 5 years) | 
| Overall Survival | Overall survival time was defined as the number of months from registration to the date of death or last follow-up | Time from registration to death or last follow up (up to 5 years) | 
| Median Duration of Response | Duration of response was defined as for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response or partial response to the date progression is documented. | Up to 5 years | 
| Number of Participant With Previous Treatment of Anti-HER2 With Cardiac Events |  | Up to 5 years |