Bevacizumab Plus Vinorelbine in Treating Patients With Stage IV Breast Cancer

A Phase II Study of Bevacizumab in Combination With Vinorelbine in Stage IV Breast Cancer

Phase II trial to study the effectiveness of bevacizumab combined with vinorelbine in treating patients who have stage IV breast cancer. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody with chemotherapy may kill more cancer cells

Study Overview

• Status: Completed
• Conditions: Male Breast Cancer; Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: bevacizumab; Drug: vinorelbine tartrate

Detailed Description

OBJECTIVES:

I. Determine the complete and partial response rates in patients with stage IV breast cancer treated with concurrent bevacizumab and vinorelbine.

II. Determine the side effects of this regimen in these patients. III. Determine the time to disease progression in patients treated with this regimen.

IV. Determine the time on study (a reflection of time to progression, treatment-related side effects, and patient preference) of patients treated with this regimen.

V. Assess urine protein/creatinine ratio and serum complement levels as screening measures for renal injury in patients treated with bevacizumab.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes once every other week and vinorelbine IV over 6-10 minutes once weekly for 8 weeks. Treatment repeats every 8 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease after completion of the fourth course may receive additional courses of concurrent bevacizumab and vinorelbine administered once every other week or may continue therapy on the schedule as above.

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study within 1 year.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed stage IV breast cancer

  • Patients without pathologic or cytologic confirmation of metastatic disease must have unequivocal evidence of metastasis by physical exam or radiologic study

• Must meet 1 of the following criteria:

  • Received 1 or 2 prior conventional chemotherapy regimens for metastatic disease
  • Relapsed within 1 year after adjuvant chemotherapy and no prior chemotherapy for metastatic disease

• At least 1 unidimensionally measurable lesion, meeting 1 of the following criteria:

  • At least 20 mm by conventional techniques
  • At least 10 mm by spiral CT scan
• No CNS metastases by CT scan or MRI within the past 6 weeks
• No prior or concurrent primary CNS tumor on physical exam
• Disease progression after bone marrow or peripheral blood stem cell transplantation allowed
• HER2-positive tumors allowed if previously treated with trastuzumab (Herceptin)

• Hormone receptor status:

  • Not specified
• Male or female
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• More than 3 months
• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm^3
• No prior bleeding diathesis or coagulopathy
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN
• INR no greater than 1.5
• Creatinine less than 2 mg/dL
• Urine protein no greater than +1 by dipstick
• Urine protein less than 500 mg by 24-hour urine collection
• LVEF at least 50%
• No prior stroke
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication, including atrial fibrillation requiring systemic anticoagulation
• No grade II or greater peripheral vascular disease within the past year
• No clinically significant peripheral artery disease
• No deep vein thrombosis or embolism within the past 5 years

• No arterial thromboembolic event within the past 6 months, including any of the following:

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina
  • Myocardial infarction
• No other significant cardiovascular disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No evidence of seizures not controlled with standard medical therapy
• No prior allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in the study
• Prior mild infusion reaction to trastuzumab allowed
• No serious non-healing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 4 weeks
• No other concurrent illness (such as active infection) that would require active treatment or preclude study
• No psychiatric illness or social situation that would preclude study
• See Disease Characteristics
• No prior bevacizumab
• No other prior experimental angiogenesis inhibitors
• At least 2 weeks since prior trastuzumab and recovered
• Concurrent epoetin alfa or filgrastim (G-CSF) allowed
• See Disease Characteristics
• At least 2 weeks since prior chemotherapy and recovered
• No prior vinorelbine
• No more than 2 prior conventional chemotherapy regimens for metastatic breast cancer
• Prior hormonal therapy allowed
• At least 1 week since prior radiotherapy and recovered
• No concurrent radiotherapy
• At least 4 weeks since prior major surgical procedure or open biopsy
• At least 1 week since prior fine-needle aspiration except in the breast
• No concurrent major surgical procedure
• Recovered from the toxic effects of any prior therapy
• At least 10 days since prior oral or parenteral anticoagulants (e.g., heparin or warfarin) except to maintain the patency of permanent, indwelling central venous catheter
• At least 10 days since prior thrombolytic agents
• No chronic aspirin therapy greater than 325 mg per day or non-steroidal anti-inflammatory medications that inhibit platelet function
• No concurrent COX-2 inhibitors that inhibit platelet function
• No other concurrent investigational or commercial agents or therapies for the malignancy
• No concurrent antiretroviral therapy for HIV-positive patients
• No concurrent ketoconazole, zidovudine, or macrolide antibiotics
• No concurrent oral or parenteral anticoagulants except to maintain patency of permanent, indwelling central venous catheter
• No concurrent thrombolytic agent
• Concurrent bisphosphonates allowed
• Concurrent celecoxib or rofecoxib allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (bevacizumab, vinorelbine tartrate); Patients receive bevacizumab IV over 30-90 minutes once every other week and vinorelbine IV over 6-10 minutes once weekly for 8 weeks. Treatment repeats every 8 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease after completion of the fourth course may receive additional courses of concurrent bevacizumab and vinorelbine administered once every other week or may continue therapy on the schedule as above.

Other: laboratory biomarker analysis; Correlative studies; Biological: bevacizumab; Given IV; Other Names: Avastin; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; rhuMAb VEGF; Drug: vinorelbine tartrate; Given IV; Other Names: Eunades; navelbine ditartrate; NVB; VNB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate to combination therapy with bevacizumab and vinorelbine, defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression	Time from the first treatment on study until the time of documented disease progression, assessed up to 6 years
Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0	Up to 6 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Harold Burstein, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: June 11, 2003
• First Posted (Estimate): June 12, 2003

Study Record Updates

• Last Update Posted (Estimate): January 17, 2013
• Last Update Submitted That Met QC Criteria: January 16, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibodies; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Vinorelbine
• Other Study ID Numbers: NCI-2012-02388; 01-013; CDR0000068685 (Registry Identifier: PDQ (Physician Data Query))