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

Loyola University

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Treatments

Biological: bevacizumab

Drug: Carboplatin

Drug: ABI-007

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00654836

200027

Details and patient eligibility

About

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.

Full 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 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.

Enrollment

32 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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