Bevacizumab in Combination With Vinorelbine and Trastuzumab for HER2-Positive, Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Genentech, Inc.
New Hampshire Oncology-Hematology PA
Lowell General Hospital
Hartford Hospital
Information provided by (Responsible Party):
Harold J. Burstein, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00670982
First received: April 29, 2008
Last updated: March 29, 2013
Last verified: March 2013
  Purpose

The purpose of this research study is to determine the effects of the combination of bevacizumab, vinorelbine, and trastuzumab on participants and their cancer.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab
Drug: vinorelbine
Drug: trastuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Bevacizumab in Combination With Vinorelbine and Trastuzumab for HER2-Positive, Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Proportion of Patients Alive and Without Progression of Disease at 1 Year From Start of Protocol-based Therapy. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of patients on study without progression at one year after first treatment on study.The date of progression was defined as the earliest occurence of any of the following events: progressive disease by RECIST v1.0, date of initiation of new anticancer therapy, or death due to any cause. New anticancer therapy was defined as the addition or initiation of any new agent for treatment of cancer not including trastuzumab, vinorelbine or bevacizumab.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) and assessed by computed tomography.Complete response (CR), disappearance of all target and non-target lesions; partial response (PR), >/=30% decrease in the sum of longest dimensions of target lesions; objective response rate = CR + PR.

  • Progression-free Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Median progression free survival measured in months


Enrollment: 29
Study Start Date: May 2008
Study Completion Date: December 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: First line treatment
Patients with no prior therapy for metastatic breast cancer will receive bevacizumab intravenously every 2 weeks and vinorelbine intravenously once per week, and trastuzumab intravenously once per week
Drug: bevacizumab
Given intravenously every 2 weeks
Other Name: Avastin
Drug: vinorelbine
Given intravenously once a week
Other Name: Navelbine
Drug: trastuzumab
Given intravenously once a week
Other Name: Herceptin
Experimental: Second line treatment
Patients with 1 prior line for metastatic breast cancer will receive bevacizumab intravenously every two weeks, vinorelbine intravenously once per week, and trastuzumab intravenously once per week.
Drug: bevacizumab
Given intravenously every 2 weeks
Other Name: Avastin
Drug: vinorelbine
Given intravenously once a week
Other Name: Navelbine
Drug: trastuzumab
Given intravenously once a week
Other Name: Herceptin

Detailed Description:
  • Participants will receive bevacizumab intravenously every 2 weeks. They will also receive trastuzumab and vinorelbine intravenously once a week. Therefore, treatments will alternate between receiving all three drugs (1st week, third week, fifth week, etc.) and receiving only trastuzumab and vinorelbine (2nd week, fourth week, sixth week, etc.) A treatment cycle lasts four weeks.
  • During all treatment cycles a physical exam will be performed and the participant will be asked general health and specific questions about any problems they are experiencing.
  • X-ray, CT scans, and/or MRI scans will be performed every 8 weeks (every 2 cycles) in order to assess the effect of the study treatment on the participants cancer. These tests are considered standard of care in patients receiving chemotherapy.
  • Once a week blood counts will be performed and at least every 4 weeks, chemistry and other tests to measure any additional effect of the study drug and disease status will be checked. These tests are also considered standard of care for patients receiving chemotherapy.
  • At the beginning of the study and at the 4- and 8-week time point, additional blood will be drawn in order to conduct research blood tests to measure the presence of cancer cells in the blood.
  • A urine test and MUGA scan or echocardiogram will be done every 8 weeks while the participant in on the study.
  • Participants can remain on the research study as long as the study treatment appears to be working and they are not experiencing unacceptable side effects.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast cancer, with metastatic disease.
  • HER2-positive tumor
  • Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan
  • 18 years of age or older
  • Life expectancy of more than 12 weeks
  • ECOG Performance Status of 0 or 1
  • Normal organ and marrow function as outlined in the protocol
  • Left ventricular ejection fraction 50% or greater as determined by RVG or echocardiogram within 30 days prior to initiation of protocol therapy
  • Patients with stable or previously treated CNS metastases are eligible for study participation, provided there is no history of clinically significant CNS bleeding
  • Men and women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation

COHORT A:

  • No prior chemotherapy for treatment of metastatic breast cancer
  • May NOT have received prior treatment with trastuzumab for recurrent or metastatic breast cancer
  • No prior vinorelbine for treatment of breast cancer
  • No prior bevacizumab for treatment of breast cancer
  • May have received prior radiation therapy and/or any number of lines of hormonal therapy
  • Prior trastuzumab therapy in the adjuvant setting is also allowed, providing that relapse occured at least 12 months following the last dose
  • Must have recovered from all reversible toxicities related to prior therapy and may not have any pre-existing treatment-related toxicities in excess of Grade 1. Patients must have stopped prior radiation therapy at least 7 days prior to beginning protocol treatment

COHORT B:

  • One prior line of chemotherapy for treatment of metastatic breast cancer or recurrence of breast cancer within 12 months of completion of adjuvant trastuzumab
  • No prior vinorelbine for treatment of breast cancer
  • No prior bevacizumab for treatment of breast cancer
  • May have received prior radiation therapy and/or any number of lines of hormonal therapy
  • Must have recovered from all reversible toxicities related to prior therapy and may not have any pre-existing treatment-related toxicities in excess of Grade 1. Patients must have stopped prior radiation therapy at least 7 days prior to beginning protocol treatment

Exclusion Criteria:

  • Patients who have had chemotherapy within 14 days prior to entering the study, ot those who have not recovered adequately from adverse events due to agents administered earlier
  • Concurrent radiation therapy
  • History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in this study
  • Prior therapy with bevacizumab or vinorelbine
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
  • Inadequately controlled hypertension
  • Prior history of hypertensive crisis of hypertensive encephalopathy
  • NHYA Grade II or greater congestive heart failure
  • History of myocardial infarction of unstable angina within 6 months prior to study enrollment
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Progressive or untreated CNS metastases
  • Significant vascular disease within 6 months prior to study enrollment
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious non-healing wound, active ulcer, or untreated bone fracture
  • Proteinuria at screening
  • Pregnant or lactating
  • Current and ongoing treatment with full-dose warfarin or its equivalent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670982

Locations
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06101
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Faulkner Hospital
Boston, Massachusetts, United States, 02130
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Lowell General Hospital
Lowell, Massachusetts, United States, 01850
United States, New Hampshire
New Hampshire Oncology-Hematology PA
Hooksett, New Hampshire, United States, 03106
Sponsors and Collaborators
Harold J. Burstein, MD, PhD
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Genentech, Inc.
New Hampshire Oncology-Hematology PA
Lowell General Hospital
Hartford Hospital
Investigators
Principal Investigator: Harold J. Burstein, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Harold J. Burstein, MD, PhD, Associate Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00670982     History of Changes
Other Study ID Numbers: 07-214
Study First Received: April 29, 2008
Results First Received: February 15, 2013
Last Updated: March 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
HER2 positive
bevacizumab
vinorelbine
trastuzumab

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Trastuzumab
Vinblastine
Vinorelbine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014