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Bevacizumab Plus Vinorelbine in Treating Patients With Stage IV Breast Cancer

Primary Purpose

Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
vinorelbine tartrate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bevacizumab, vinorelbine tartrate)

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate to combination therapy with bevacizumab and vinorelbine, defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria

Secondary Outcome Measures

Time to progression
Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0

Full Information

First Posted
June 6, 2001
Last Updated
January 16, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00017394
Brief Title
Bevacizumab Plus Vinorelbine in Treating Patients With Stage IV Breast Cancer
Official Title
A Phase II Study of Bevacizumab in Combination With Vinorelbine in Stage IV Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2001 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (bevacizumab, vinorelbine tartrate)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vinorelbine tartrate
Other Intervention Name(s)
Eunades, navelbine ditartrate, NVB, VNB
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response rate to combination therapy with bevacizumab and vinorelbine, defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Time to progression
Time Frame
Time from the first treatment on study until the time of documented disease progression, assessed up to 6 years
Title
Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time Frame
Up to 6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harold Burstein
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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Bevacizumab Plus Vinorelbine in Treating Patients With Stage IV Breast Cancer

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