VEGF Trap in Treating Patients With Metastatic Breast Cancer

Phase 2

Completed

Conditions: Metastatic Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer

Interventions: Biological: ziv-aflibercept

Registration Number: NCT00369655

Lead Sponsor: National Cancer Institute (NCI)

Brief 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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (ziv-afibercept)	ziv-aflibercept	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Confirmed Tumor Response	Up to 5 years	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.
Proportion of Patients Receiving Vascular Endothelial Growth Factor (VEGF) Trap With 6-month Progression-free Survival	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participant With Previous Treatment of Anti-HER2 With Cardiac Events	Up to 5 years
Progression Free Survival	Time from registration to disease progression or death (up to 5 years)	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.
Overall Survival	Time from registration to death or last follow up (up to 5 years)	Overall survival time was defined as the number of months from registration to the date of death or last follow-up
Median Duration of Response	Up to 5 years	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.