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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Loyola University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Loyola University
ClinicalTrials.gov Identifier:
NCT00654836
First received: April 8, 2008
Last updated: October 29, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Breast Cancer
Biological: bevacizumab
Drug: carboplatin
Drug: ABI-007l albumin-stabilized nanoparticle formulation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Loyola University:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    Treatment will continue until disease progression.


Secondary Outcome Measures:
  • Response rate [ Time Frame: every 63 days ] [ Designated as safety issue: No ]
    The cycle length is 63 days. Treatment will continue until disease progression

  • Overall survival [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    Patients will be followed for a maximum of 2 years after progression or until death

  • Toxicity profile [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 72
Study Start Date: October 2007
Estimated Study Completion Date: February 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carboplatin, ABI-007 and Bevacizumab Biological: bevacizumab
Bevacizumab 15mg/kg on Days 1,22, 43.
Drug: carboplatin
Carboplatin AUC 6 Day 1, 22, 43.
Drug: ABI-007l albumin-stabilized nanoparticle formulation
ABI-007 100mg/m2 Days 1,8, 15, 22, 29, 36,43,50.

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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 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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

  • 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
  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: NCT00654836

Locations
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.
Investigators
Principal Investigator: Shelly Lo, MD Loyola University
  More Information

Additional Information:
No publications provided

Responsible Party: Loyola University
ClinicalTrials.gov Identifier: NCT00654836     History of Changes
Other Study ID Numbers: CDR0000593048, LUMC-LU200027, ABRAXIS-LU200027
Study First Received: April 8, 2008
Last Updated: October 29, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Carboplatin
Paclitaxel
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 22, 2014