Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase II Safety and Tolerability Study of Bevacizumab When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00476827
Recruitment Status : Terminated (Slow accrual)
First Posted : May 22, 2007
Results First Posted : July 17, 2013
Last Update Posted : July 17, 2013
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE May 18, 2007
First Posted Date  ICMJE May 22, 2007
Results First Submitted Date December 10, 2012
Results First Posted Date July 17, 2013
Last Update Posted Date July 17, 2013
Study Start Date  ICMJE May 2007
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2013)
  • Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 3.0) Toxicity Reporting Criteria. [ Time Frame: May 2009 ]
    Primary endpoint has not been analysed secondary to slow and low accrual numbers.
  • Determining the Safety and Tolerability of Adding Avastin to Single Agent Chemotherapy to Treat Patients With Brain Metastasis Originating From Breast Cancer [ Time Frame: trial closure ]
    Due to slow accrual study was prematurely closed and endpoint not analysed
Original Primary Outcome Measures  ICMJE
 (submitted: May 21, 2007)
• Safety and Tolerability In this study, safety and tolerability will be assessed according to standard (CTCAE version 3.0) toxicity reporting criteria. Adverse events will be monitored at every patient visit and quality of life will be measured at ba [ Time Frame: May 2009 ]
Change History Complete list of historical versions of study NCT00476827 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2013)
  • Assess the Activity of Avastin When Added to Single Agent Chemotherapy, as Measured by Radiographic Response Rate,Progression Free Survival, and Overall Survival. [ Time Frame: 8 to 9 weeks ]
    Due to slow accrual study was prematurely closed and endpoint not analysed
  • To Assess the Quality of Life During Treatment With This Therapeutic Approach [ Time Frame: 8 to 9 weeks ]
    Due to slow accrual study was prematurely closed and endpoint not analysed
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Safety and Tolerability Study of Bevacizumab When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain
Official Title  ICMJE A Phase II Safety and Tolerability Study of Avastin When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain
Brief Summary Our hypothesis is that this study design, in which bevacizumab is added to one of six single agent chemotherapies with proven activity in metastatic breast cancer, will result in regression or stabilization of this disease in a safe and tolerable manner.
Detailed Description

There is an unmet clinical need for effective therapy of breast cancer that has metastasized to the brain. In this scenario, median survival is around 12 months using currently available therapeutic interventions. The majority of chemotherapy-based clinical trials have considered the presence of central nervous system metastasis an exclusion criterion due to the risk of toxicities, the inability of chemotherapeutic agents to cross the blood brain barrier, and the limited overall survival within this patient population.

The preclinical data regarding the safety and activity of bevacizumab in vascular endothelial growth factor(VEGF)-expressing tumors provide a good rationale for its study in patients with breast cancer with metastasis to the brain. Yano, et al. illustrated that tumor cell expression of VEGF messenger ribonucleic acid and protein directly correlated with angiogenesis and growth of brain metastasis in a nude mouse model. Transfecting the experimental cell lines known to produce visceral metastasis with an anti-sense VEGF-gene significantly reduced the incidence of brain metastasis. Kim, et al. illustrated that a murine model specific for brain metastases originating from breast cancer showed elevated expression of the angiogenic and permeability-inducing factor VEGF-A. The growth of the brain metastases in this model was attenuated by the addition of a VEGF-tyrosine kinase inhibitor via induction of apoptosis and decreased angiogenesis. VEGF has also been implicated in the development of brain edema, a significant source of the morbidity and mortality associated with brain metastasis. Enhanced levels of VEGF and its receptors have been reported in a murine model after induction of cortical ischemia. Finally, antagonism of VEGF was demonstrated to reduce both immediate and delayed volume of infarct.

The optimal dose of bevacizumab has been extensively studied in phase I trials alone and in combination with chemotherapy. The safe and effective dose has been established as 10 mg/kg q 14 days or 15 mg/kg Q 21 days. In addition to irinotecan and paclitaxel, it has been previously used in phase II/III settings in combination with capecitabine, vinorelbine, gemcitabine, and docetaxel. Phase III studies showed an overall survival advantage when bevacizumab was added to an irinotecan/Fluorouracil (5FU)-based regimen for metastatic colorectal cancer, and when added to weekly paclitaxel for metastatic breast cancer.

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Bevacizumab
    Bevacizumab(Avastin) 15 mg/kg every 3 weeks in combination with Capecitabine (Xeloda), 2 weeks on and 1 week off on a every 3 week cycle. until progression or unacceptable toxicity develops
    Other Name: Avastin
  • Drug: Docetaxel
    Docetaxel 35mg/m² IV over 60 min days 1, 8, and 15 in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle. until progression or unacceptable toxicity develops
    Other Name: Taxotere
  • Drug: CPT-11
    CPT-11 (Irinotecan, Camptosar) - Patients being treated with an enzyme inducing antiepileptic drug (EIAED) will receive 340 mg/m² IV; others will receive 125 mg/m² IV 90 min on days 1 and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.until progression or unacceptable toxicity develops
    Other Names:
    • Irinotecan
    • Camptosar
  • Drug: Paclitaxel
    Paclitaxel (Taxol)90 mg/m2 IV over 60-90 min days 1, 8, and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.until progression or unacceptable toxicity develops
    Other Name: Taxol
  • Drug: Vinorelbine Tartrate
    Vinorelbine Tartrate (Navelbine®) 25 mg/m² IV over 10 min days 1, 8 and 15 in combination with avastin 10 mg/kg IV on days 1 and 15 of a 28-day cycle. until progression or unacceptable toxicity develops
    Other Name: Navelbine®
  • Drug: Gemcitabine
    Gemcitabine (difluorodeoxycytidine, dFdC) 1000 mg/m2 IV on days 1 and 8 in combination with avastin 15 mg/kg IV on day 1 of a 21-day treatment cycle.until progression or unacceptable toxicity develops
    Other Name: difluorodeoxycytidine
Study Arms
  • Active Comparator: Bevacizumab / Capecitabine
    Bevacizumab 15 mg/kg every 3 weeks in combination with Capecitabine (Xeloda), 2 weeks on and 1 week off on a every 3 week cycle.
    Intervention: Drug: Bevacizumab
  • Active Comparator: Bevacizumab / Docetaxel
    Docetaxel (taxotere) 35mg/m² IV over 60 min days 1, 8, and 15 in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
    Intervention: Drug: Docetaxel
  • Active Comparator: Bevacizumab /Irinotecan (Camptosar®, CPT-11)
    CPT-11 (Irinotecan, Camptosar) - Patients being treated with an enzyme inducing antiepileptic drug (EIAED) will receive 340 mg/m² IV; others will receive 125 mg/m² IV 90 min on days 1 and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
    Intervention: Drug: CPT-11
  • Active Comparator: Bevacizumab / Paclitaxel
    Paclitaxel (Taxol)90 mg/m2 IV over 60-90 min days 1, 8, and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
    Intervention: Drug: Paclitaxel
  • Active Comparator: Bevacizumab /Vinorelbine Tartrate
    Vinorelbine Tartrate (Navelbine®) 25 mg/m² IV over 10 min days 1, 8 and 15 in combination with avastin 10 mg/kg IV on days 1 and 15 of a 28-day cycle.
    Intervention: Drug: Vinorelbine Tartrate
  • Active Comparator: Bevacizumab / Gemcitabine
    Gemcitabine (difluorodeoxycytidine, dFdC) 1000 mg/m2 IV on days 1 and 8 in combination with avastin 15 mg/kg IV on day 1 of a 21-day treatment cycle.
    Intervention: Drug: Gemcitabine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 4, 2011)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2007)
59
Actual Study Completion Date May 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female, 18+, with evaluable metastatic breast cancer and stable brain metastases
  • Must have received definitive radiotherapy
  • No evidence, or history of, central nervous system hemorrhage
  • Adequate organ and hematological function

Exclusion Criteria:

  • Active infection, non-healing wound, or history of any bleeding diathesis or coagulopathy
  • Uncontrolled hypertension, congestive heart failure, peripheral vascular disease
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00476827
Other Study ID Numbers  ICMJE Pro00014926
AVF4124s
9597-07-4R0 ( Other Identifier: Duke IRB Legacy Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Kimberly Blackwell, MD Duke University
PRS Account Duke University
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP