Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

VEGF Trap in Treating Patients With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	NCCTG-N0537 N0537, NCT00369655

Objectives

Primary

1. 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.
2. Assess the 6-month progression-free survival rate in patients treated with VEGF Trap.

Secondary

1. Describe the adverse event profile (grade using the NCI CTCAE version 3.0) of VEGF Trap in these patients.
2. Describe the progression-free survival times in patients treated with VEGF Trap.
3. Describe the overall survival of patients treated with VEGF Trap.
4. Describe the duration of response in patients treated with VEGF Trap.

Entry Criteria

Disease Characteristics:

• 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

   [Note: *Patients relapsing while receiving or within 6 months of completing neoadjuvant or adjuvant chemotherapy are considered to have disease progression on 1 regimen for metastatic disease]




• 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

Prior/Concurrent Therapy:

• 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

Patient Characteristics:

• 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

Expected Enrollment

A total of 45 patients will be accrued for this study.

Outcomes

Tumor response rate as measured by RECIST criteria
Progression-free survival rate at 6 months

Adverse event profile as assessed by NCI CTCAE version 3.0
Time to disease progression
Overall survival
Duration of response

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.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Edith Perez, MD, Protocol chair		Ph: 507-284-1159 Email: perez.edith@mayo.edu
Kendrith Rowland, MD, Protocol co-chair		Ph: 217-383-4083 Email: kendrith.rowland@carle.com
Donald Northfelt, MD, FACP, Protocol co-chair		Ph: 480-301-8335 Email: northfelt.donald@mayo.edu

Registry Information
Official Title		Phase II Trial of VEGF Trap in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and/or Taxane
Trial Start Date		2007-01-12
Trial Completion Date		2007-12-15 (estimated)
Registered in ClinicalTrials.gov		NCT00369655
Date Submitted to PDQ		2006-06-07
Information Last Verified		2008-11-24
NCI Grant/Contract Number		CA25224