Carboplatin, Paclitaxel, and Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

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. Identifier: NCT00654836
Recruitment Status : Completed
First Posted : April 9, 2008
Results First Posted : September 14, 2017
Last Update Posted : September 14, 2017
Genentech, Inc.
Celgene Corporation
Information provided by (Responsible Party):
Shelly Lo, Loyola University

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving carboplatin and paclitaxel together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin and paclitaxel together with bevacizumab works in treating patients with locally recurrent or metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: bevacizumab Drug: Carboplatin Drug: ABI-007 Phase 2

Detailed Description:



  • To determine the progression-free survival of patients with locally recurrent or metastatic breast cancer treated with carboplatin, paclitaxel albumin-stabilized nanoparticle formulation, and bevacizumab as first-line therapy.


  • To determine the response rate in these patients.
  • To determine the overall survival of these patients.
  • To evaluate the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive carboplatin IV over 1 hour and bevacizumab IV on days 1, 22 and 43. Patients also receive paclitaxel albumin-bound nanoparticle formulation IV over 30 minutes on days 1, 8 ,15, 22, 29, 36, 43, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded archived tumor tissue samples are assessed by immunohistochemistry (IHC) for various biomarkers. Levels of Notch-1, Notch-4, cyclin A, cyclin B, Jagged-1, and DLL4 in tumor-associated endothelial cells are correlated with response in both estrogen- and progesterone-positive and negative tumors, and independently of p53 status.

After completion of study treatment, patients are followed for up to 2 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Carboplatin, Nanoparticle Albumin-Bound Paclitaxel (ABI-007) and Avastin as the First Line Therapy in Metastatic Breast Cancer.
Study Start Date : October 2007
Actual Primary Completion Date : February 2012
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Carboplatin, ABI-007 and Bevacizumab
Participants will receive combination carboplatin, nanoparticle albumin-bound paclitaxel (ABI-007-Abraxane), and bevacizumab (Avastin)
Biological: bevacizumab
Participants will receive bevacizumab 15 mg/kg on days 1,22, and 43.
Other Name: Avastin

Drug: Carboplatin
Participants will receive a standard carboplatin dose according to their area under the plasma drug concentration-time curve (AUC-6) on days 1, 22, and 43.
Other Name: Paraplatin

Drug: ABI-007
Participants will receive ABI-007 (Abraxane) 100mg/m2 on days 1,8, 15, 22, 29, 36,43,and 50.
Other Name: Abraxane

Primary Outcome Measures :
  1. Progression-free Survival [ Time Frame: 30 Months ]
    Progression-free survival was measured from treatment initiation to 30 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures :
  1. Response Rate at End of Treatment [ Time Frame: 30 Months ]
    Response to treatment was recorded 30 months following treatment initiation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions .

  2. Overall Survival [ Time Frame: 80 Months ]
    Overall survival was measured from treatment initiation to 80 months

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed primary adenocarcinoma of the breast

    • Locally recurrent or metastatic disease
  • Must have HER-2-negative breast cancer or, if HER-2-positive, must be unable to receive trastuzumab (Herceptin®) or have previously received trastuzumab in the past
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or as > 10 mm by spiral CT scan.
  • No known CNS disease
  • Hormone receptor status not specified


Inclusion criteria:

  • Postmenopausal status not specified
  • ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • Total bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastasis is present in the absence of liver metastasis)
  • Creatinine ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent malignancies within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Exclusion criteria:

  • Pre-existing neuropathy ≥ grade 1
  • Uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Serious, non-healing wound, ulcer, or bone fracture
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications)
  • History of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association class II-IV congestive heart failure
  • History of myocardial infarction or unstable angina within the past 6 months
  • History of stroke or transient ischemic attack within the past 6 months
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Significant traumatic injury within the past 28 days
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • Proteinuria, as demonstrated by either urine protein:creatinine ratio ≥ 1.0 OR urine dipstick for proteinuria ≥ 2+

    • Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline must demonstrate 24-hour urine protein ≤ 1g
  • History of allergy or hypersensitivity to paclitaxel albumin-stabilized nanoparticle formulation, paclitaxel, bevacizumab, carboplatin, albumin, drug product excipients, or chemically similar agents


  • See Disease Characteristics
  • Recovered from all prior therapy
  • No prior chemotherapy for locally recurrent or metastatic disease
  • Prior neoadjuvant or adjuvant chemotherapy allowed
  • More than 1 week since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device
  • More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
  • More than 4 weeks since prior radiotherapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 1 year since prior taxane regimen
  • No other concurrent investigational agents
  • Concurrent anticoagulation allowed, provided the following criteria are met:

    • Stable dose of warfarin or low molecular weight heparin
    • INR within desired range (2-3)
    • No evidence of active bleeding or coagulopathy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent radiotherapy, chemotherapy, immunotherapy, or antitumor hormonal therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00654836

United States, Illinois
Good Samaritan Cancer Care Center at Advocate Good Samaritan Hospital
Downers Grove, Illinois, United States, 60515-1500
Delnor Community Hospital - Geneva
Geneva, Illinois, United States, 60134-4200
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Edward Hospital Cancer Center
Naperville, Illinois, United States, 60540
Swedish-American Regional Cancer Center
Rockford, Illinois, United States, 61104-2315
Central Dupage Cancer Center
Winfield, Illinois, United States, 60190-1295
Sponsors and Collaborators
Loyola University
Genentech, Inc.
Celgene Corporation
Principal Investigator: Shelly Lo, MD Loyola University

Responsible Party: Shelly Lo, Associate Professor, Loyola University Identifier: NCT00654836     History of Changes
Other Study ID Numbers: 200027
First Posted: April 9, 2008    Key Record Dates
Results First Posted: September 14, 2017
Last Update Posted: September 14, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Shelly Lo, Loyola University:
recurrent breast cancer
stage III breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors