Clinical trial NCT00472693: Bevacizumab and Abraxane as Second-line Therapy in Triple Negative Metastatic Breast Cancer
Official title: A Phase II Trial of Bevacizumab and ABI-007 (Abraxane) as Second-line Therapy in Her-2 Negative, Hormone Receptor Negative Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer
Metastatic breast cancer
Second-Line Therapy
Triple Negative
Her-2 negative
Hormone receptor negative
Abraxane
Bevacizumab
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2007-05-14
Enrollment: 5
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the addition of bevacizumab to Abraxane as second-line therapy in Her-2 negative, hormone receptor negative metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

* Female, aged 18 years or older and able to give informed consent.
* Histologically- or cytologically-proven adenocarcinoma of the breast at time of first diagnosis
* ECOG performance status 0 or 1
* Life expectancy \> 12 weeks
* Stage IV disease and have at least one lesion measurable by standard RECIST criteria
* Disease progression after at least one prior chemotherapy regimen for metastatic disease or within 12 months of adjuvant chemotherapy initiation.
* All chemotherapy must be stopped \> 2 weeks before enrollment.
* Primary or metastatic tumor must be negative for estrogen and progesterone receptor expression. Testing must be done in a CLIA-approved laboratory.
* Primary or metastatic tumor must have 0 or 1+ staining for HER2/neu identified immunohistochemically (IHC), by an approved method using one of the standard monoclonal or polyclonal antibodies (HercepTest, cb-11, PAb1, or TAB250), or if FISH status is known, it must be negative. Testing must be done in a CLIA-approved laboratory.
* Left ventricular ejection fraction must be \>= institutional lower limit of normal as determined by MUGA or echocardiogram
* Patient must be able to comply with treatment and follow-up procedures:
* Adequate bone marrow, liver and renal function; Absolute neutrophil count \>= 1500/mm3; Hemoglobin \>= 10 g/dl; Platelet count \>= 100,000/mm3; Creatinine \<= 2.0; PTT and either INR or PT \< 1.5x normal; Total bilirubin \<= 1.5 X upper limit of normal; AST, ALT, and alkaline phosphatase \<= 2 X upper limit of normal (or \<= 5X upper limit of normal if known liver metastases)
* If female is of childbearing potential, pregnancy test must be negative and patient must be willing to use effective contraception while on treatment and for at least 3 months after the last dose of study medication

Exclusion Criteria:

* Prior treatment with VEGF targeted therapy
* Prior taxane therapy for metastatic disease or for adjuvant therapy within the previous 12 months
* History of prior cancer, excluding carcinoma in situ of the cervix and non-melanoma skin cancers
* Known CNS disease
* Inadequately controlled hypertension (defined as systolic blood pressure\>150 and/or diastolic blood pressure\>100 mmHg on antihypertensive medications)
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or unstable angina within 6 months prior to study enrollment
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
* Symptomatic peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
* Serious, non-healing wound, ulcer or bone fracture
* Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio \>1.0 at screening OR Urine dipstick for proteinuria \>2+ (patients discovered to have \>2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \<1g of protein in 24 hours to be eligible)
* Patients with active infection
* Women who are pregnant or lactating
* Radiation therapy within 3 weeks of study entry
* Patients with hypersensitivity to ABI-007, Chinese hamster ovary cell products, or other recombinant human antibodies
* Baseline neuropathy \> grade 2
* Participation in an investigational study of an antineoplastic agent within 4 weeks of first infusion of this study.

Primary outcomes:
measure: To determine progression-free survival among women receiving bevacizumab + ABI-007 given as second-line combination therapy for hormone receptive negative, Her-2 negative metastatic breast cancer.
timeFrame: Study Completion
Secondary outcomes:
measure: To determine the overall response rate to bevacizumab + ABI-007 in this study population.
timeFrame: Study completion
measure: To determine the toxicity of bevacizumab + ABI-007 in this study population.
timeFrame: Study completion
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center at University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center of University of Pennsylvania
name: Angela DeMichele, M.D.
role: PRINCIPAL_INVESTIGATOR
References: