Clinical trial NCT00733408: Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer
Official title: Combined Targeted Therapies for Triple Negative Advanced Breast Cancer - A Phase II Trial of Weekly Nab-Paclitaxel and Bevacizumab Followed by Maintenance Targeted Therapy With Bevacizumab and Erlotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Triple-negative Breast Cancer
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-08-13
Enrollment: 59
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well giving paclitaxel albumin-stabilized nanoparticle (Nab-paclitaxel) formulation together with bevacizumab followed by bevacizumab and erlotinib hydrochloride work in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as 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 prevent cancer growth by blocking the ability of cancer cells to grow and spread. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial evaluates a maintenance treatment with erlotinib and bevacizumab after Nab-paclitaxel and bevacizumab which may control cancer growth with biologic therapies.

Detailed description: PRIMARY OBJECTIVES:

I. Progression free survival.

SECONDARY OBJECTIVES:

I. Response rate.

II. Overall survival.

III. Safety and toxicity.

IV. Exploratory biomarkers will be assessed as potential predictors of response to treatment including: expression of epidermal growth factor receptor (EGFR) and secreted protein acidic and rich in cysteine (SPARC) in the primary tumor and changes in levels of circulating tumor cells (CTCs) and circulating endothelial cells (CECs).

OUTLINE:

INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up per physician discretion.

Eligibility criteria: Inclusion Criteria:

* Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=\< 10%), progesterone receptor (PR) negative (=\< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=\< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
* Be receiving first-line therapy for metastatic disease
* Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration
* OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL
* Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment
* Bilirubin =\< 1.5 mg/dL
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
* Alkaline phosphatase =\< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
* Platelets \> 100,000 cells/mm\^3
* Hemoglobin \> 9.0 g/dL
* Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
* Creatinine =\< 1.5 mg/dL is recommended; however, institutional norms are acceptable
* If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy
* Pre-existing peripheral neuropathy, if present, must be \< grade 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0)
* Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines

Exclusion Criteria:

* Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane
* Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids
* Pre-existing nephritic syndrome
* Serious intercurrent medical or psychiatric illness including serious active infection
* 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 must have a UPC ratio done that is \< 1.0 to be eligible; if the UPC ratio is \>= 1.0 then the patient should undergo a 24-hour urine collection which must demonstrate =\< 1 g of protein in 24 hours for the patient to be eligible)
* Known hypersensitivity to any component of bevacizumab or to nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation)

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Time from date of registration to date of death due to any cause, assessed up to 8 years
measure: Percentage of Participants With Response
timeFrame: Up to 8 years
measure: Incidence of Adverse Events as Assessed by National Cancer Institute CTCAE Version 3.0
timeFrame: Up to 30 days after treatment discontinuation
measure: EGFR and SPARC Expression in the Primary Tumor
timeFrame: Up to 8 years
measure: Changes in Levels of Circulating Tumor Cells
timeFrame: Baseline to up to 8 years
measure: Changes in Levels of Circulating Endothelial Cells
timeFrame: Baseline to up to 8 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Anchorage Oncology Centre
state: Alaska
city: Anchorage
country: United States
facility: Katmai Oncology Group
state: Alaska
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Yuma
country: United States
facility: Yuma Cancer Center
state: Arizona
city: Lewiston
country: United States
facility: Saint Joseph Regional Medical Center
state: Idaho
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Kirkland
country: United States
facility: Evergreen Hospital Medical Center
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital Regional Cancer Care Center
state: Washington
city: Redmond
country: United States
facility: Group Health Cooperative, Redmond
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
city: Sequim
country: United States
facility: Olympic Medical Cancer Care Center
state: Washington
city: Spokane
country: United States
facility: Spokane Valley Cancer Center-Mayfair
state: Washington
city: Tacoma
country: United States
facility: Multicare Medical Oncology Hematology
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Jennifer Specht
role: PRINCIPAL_INVESTIGATOR
References: