VEGF Trap in Treating Patients With Metastatic Breast Cancer
Condition: Metastatic Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: ziv-aflibercept
Intervention MeSH terms: Aflibercept; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        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