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Phase II Study With Abraxane, Bevacizumab and Carboplatin in Triple Negative Metastatic Breast Cancer (ABC)

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: NCT00479674
Recruitment Status : Completed
First Posted : May 28, 2007
Results First Posted : February 18, 2015
Last Update Posted : February 18, 2015
Sponsor:
Collaborators:
Genentech, Inc.
Celgene Corporation
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE May 25, 2007
First Posted Date  ICMJE May 28, 2007
Results First Submitted Date  ICMJE December 9, 2014
Results First Posted Date  ICMJE February 18, 2015
Last Update Posted Date February 18, 2015
Study Start Date  ICMJE May 2007
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2015)
Best Clinical Response Expressed as Percentage of Participants Treated With Combination Regimen of Weekly Abraxane® and Carboplatin Plus Biweekly Bevacizumab to Treat Women With Stage IV or Inoperable Stage III "Triple Negative" Metastatic Breast Cancer. [ Time Frame: 5 years ]
Best clinical response is based on RECIST criteria, the proportion in each response category along with the exact binomial confidence intervals are estimated. Toxicity summaries are also provided.
Original Primary Outcome Measures  ICMJE
 (submitted: May 25, 2007)
To assess the safety and tolerability of a combination regimen of weekly Abraxane® and carboplatin plus biweekly bevacizumab to treat women with Stage IV or inoperable Stage III "triple negative" metastatic breast cancer. NCI CTCAE Version 3.0 to assess [ Time Frame: two years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2015)
  • Median Proportion Progression-free as Estimated by Kaplan-Meier Methods [ Time Frame: 5 years ]
    PFS was defined as time from trial enrollment to disease progression or death, whichever occurred first.
  • To Evaluate Sequential Plasma Samples for Presence of Selected Angiogenic Markers [ Time Frame: 18 months ]
  • to Determine if Apolipoprotein Alleles (Apo-E) Correlate With Treatment-related Neuropathy [ Time Frame: 18 months ]
  • to Determine if SPARC Expression in Breast Tumors Predicts Progression-free Survival (PFS) [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2007)
Clinical: To assess progression-free survival (PFS) in measurable disease patients according to RECIST criteria. Compare disease status with serial CT scans using RECIST Correlative: To evaluate sequential plasma samples for presence [ Time Frame: two years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study With Abraxane, Bevacizumab and Carboplatin in Triple Negative Metastatic Breast Cancer
Official Title  ICMJE A Phase II Study of Abraxane®, Carboplatin and Bevacizumab in "Triple Negative" (Demonstrating No Expression for Estrogen, Progesterone, or Her2 Receptors) Metastatic Breast Cancer
Brief Summary Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane® (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and tolerability. When combined with a taxane, platinum agents improve response in metastatic breast cancer, with carboplatin conferring less toxicity than cisplatin. Monoclonal antibodies including bevacizumab target vascular endothelial growth factor (VEGF) to reduce angiogenesis. We hypothesize that the previously-untested combination of weekly Abraxane® and carboplatin plus biweekly bevacizumab will lengthen time to progression without producing intolerable toxicity.
Detailed Description Anthracycline-based chemotherapy is widely used as adjuvant treatment for breast cancer. In addition to the challenge posed by anthracycline-induced cardiotoxicity, there are issues surrounding previous treatment with anthracyclines which limit its utility in the metastatic disease setting. Many patients with advanced disease will have had prior anthracycline-based adjuvant therapy, may have reached a maximum cumulative lifetime dose, or developed refractory disease, creating an obvious need for non-anthracycline treatment strategies.3 Platinum- and taxane-based chemotherapies as first-line therapy for metastatic breast cancer have demonstrated significant activity, producing single-agent response rates > 50%; in combination these rates increased to > 60% in both previously untreated and in patients who previously received anthracyclines.3 However, overall survival has remained relatively unchanged.4 As there is currently no standard of care for patients with metastatic breast cancer, various physical and psychological factors must be considered when evaluating chemotherapy treatment options, including the patient's tumor biology and growth rate, presence and extent of metastases, history of prior treatment and response, sensitivity and tolerance to therapy, and quality of life.2 Strategies to develop combination, higher dose, or sequential regimens using these active agents, while improving response rates and/or time to progression, may produce increased toxicity without increased survival.2 Because metastatic breast cancer remains essentially incurable using cytotoxic therapy alone, the study of targeted biologics offers new opportunities to enhance drug delivery via their ability to regulate specific receptors that are associated with clinically aggressive disease processes.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Abraxane
    100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death..
    Other Name: nanoparticle albumin-bound paclitaxel
  • Drug: Bevacizumab
    10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death.
    Other Name: Avastin
  • Drug: Carboplatin
    area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Study Arms  ICMJE Experimental: Abraxane, Carboplatin, Bevacizumab
Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15
Interventions:
  • Drug: Abraxane
  • Drug: Bevacizumab
  • Drug: Carboplatin
Publications * Not Provided

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: January 29, 2015)
41
Original Estimated Enrollment  ICMJE
 (submitted: May 25, 2007)
70
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Tissue block containing tumor to confirm metastatic breast cancer is required;
  • Measurable disease according to RECIST criteria
  • "Triple negative" disease defined as tumor demonstrating no expression for estrogen, progesterone or human epidermal growth factor receptor 2(HER2)receptors. "No expression" is categorized as ≤ 10% of cells staining or Allred ≤ 2;
  • Aged 18 years or older;
  • Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1; life expectancy ≥ 3 months;
  • Patients may have received 0 - 1 prior therapies (except taxanes in the metastatic setting). An interval of at least 1 week must have elapsed since prior chemotherapy or hormonal therapy for metastatic disease; at least 6 months must have elapsed since prior adjuvant therapy;
  • ≥ 2 weeks between surgery and study enrollment (≥ 4 weeks between major surgery (defined as open abdominal/thoracic/cardiac) and study enrollment;
  • Laboratory tests performed within 14 days of study entry:

    • Granulocytes ≥ 1,500/µL;
    • Platelets ≥ 100,000/µL;
    • Hemoglobin ≥ 9 gm/dL;
    • Total bilirubin ≤ institutional upper limit of normal (ULN);
    • Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN;

      • Alkaline phosphatase ≤ 2.5 times ULN;
    • Estimated creatinine clearance ≥ 60 mL/min.
  • left ventricular ejection fraction (LVEF)≥ 50% by multigated acquisition (MUGA)/Echocardiogram;
  • Informed consent to receive protocol treatment, to provide biologic specimens, and to complete neurotoxicity questionnaires;
  • Cognitive and communication skills to comply with study and/or follow-up procedures;
  • No reproductive potential:

    • If pre-menopausal: Negative serum pregnancy test and patient agreement to use adequate contraceptive method (abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during and for 3 months after completion of treatment.
    • If post-menopausal: Amenorrhea for ≥ 12 months.

Exclusion Criteria:

  • Pregnant or breast feeding;
  • Prior treatment with Abraxane®, carboplatin or bevacizumab, or any taxane for metastatic breast cancer;
  • Known hypersensitivity to any component of any study drug;
  • Active infection;
  • Current neuropathy ≥ grade 2;
  • central nervous system (CNS) metastases as determined by head CT with contrast;
  • History of bleeding within the past 6 months or active bleeding disorder;
  • Serious non-healing wound, ulcer or bone fracture;
  • Uncontrolled congestive heart failure (CHF), or history of myocardial infarction(MI), unstable angina, stroke, or transient ischemia within previous 6 months;
  • Inadequately controlled hypertension (defined as systolic blood pressure < 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications; prior history of hypertensive crisis or hypertensive encephalopathy;
  • Proteinuria (defined as urine protein: creatinine (UPC) ratio ≥ 1.0 or urine dipstick ≥ 2+.
  • Significant vascular disease (aortic aneurysm, aortic dissection) or symptomatic peripheral vascular disease;
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within previous 6 months;
  • Uncontrolled serious contraindicated medical condition or psychiatric illness.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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 NCT00479674
Other Study ID Numbers  ICMJE Pro00014837
AVF3962s
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE
  • Genentech, Inc.
  • Celgene Corporation
Investigators  ICMJE
Principal Investigator: Kimberly Blackwell, MD Duke University
PRS Account Duke University
Verification Date January 2015

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