Clinical trial NCT00281528: Weekly vs. Every 2 Week vs. Every 3 Week Administration of ABI-007 (Abraxane)/Bevacizumab Combination in Metastatic Breast Cancer
Official title: A Phase II Study of Weekly Versus Every 2-week Versus Every 3-week Administration of ABI-007 (Abraxane) in Combination With Bevacizumab in Women With Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Neoplasms
Neoplasm Metastasis
Keywords: First Line Metastatic Breast Cancer
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2006-01-25
Enrollment: 208
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open-label, randomized Phase II study in previously untreated patients with metastatic breast cancer to evaluate the antitumor activity and safety of weekly dose-dense ABI-007 (Abraxane) compared to 2-weekly regimen vs the standard 3-weekly infusion. All patients will also receive concurrent bevacizumab.


Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed adenocarcinoma of the breast.
* Stage IV disease
* Measurable disease
* Patients must not be a candidate for Herceptin therapy
* At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal.
* At least 4 weeks since major surgery, with full recovery.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Female \>18 years of age.
* Patient has the following blood counts at Baseline:

Absolute neutrophil count ≥ 1.5 x 10\^9cells/L; platelets ≥ 100 x 10\^9 cells/L; hemoglobin ≥ 9 g/dL.

* Patient has the following blood chemistry levels at Baseline: Aspartate transaminase (AST or SGOT), alanine aminotransferase (ALT or SGPT) ≤ 2.5x upper limit of normal range (ULN); total bilirubin ≤ ULN; creatinine ≤ 1.5 mg/dL.
* If female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug.
* If fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.
* Informed consent has been obtained.

Exclusion Criteria:

* Prior neo-adjuvant or adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies. No prior therapy for metastatic disease is allowed. If a taxane was part of the adjuvant regimen, at least 12 months should have passed from completion of taxane regimen to relapse. If a non-taxane-based adjuvant therapy was administered, at least 6 months should have passed from completion to relapse.
* Concurrent immunotherapy or hormonal therapy.
* Parenchymal brain metastases, including leptomeningeal involvement.
* Inadequately controlled hypertension (defined as blood pressure of \> 150/100 mmHg) or New York Heart Association (NYHA) Grade 2 or greater congestive heart failure.
* Any prior history of hypertensive crisis or hypertensive encephalopathy.
* 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.
* History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to study enrollment.
* 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).
* Known hypersensitivity to any component of bevacizumab.
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to first dose.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, anticipation of need for major surgical procedure during the course of the study. Serious, non-healing wound, ulcer, or bone fracture. Serious intercurrent medical or psychiatric illness, including serious active infection.
* History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
* Pregnant or nursing women.
* Sensory neuropathy of \> Grade 1 at baseline.

Primary outcomes:
measure: The Percentage of Participants Confirmed Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)
timeFrame: Up to 43 months
measure: Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)
timeFrame: up to 54 months
measure: Participant Counts of the Most Severe Grade for White Blood Cells (WBC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)
timeFrame: up to 54 months
measure: Participant Counts of the Most Severe Grade for Platelet Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)
timeFrame: up to 54 months
measure: Participant Counts of the Most Severe Grade for Hemoglobin Levels as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)
timeFrame: up to 54 months
measure: The Number of Participants With at Least One Dose Reduction for ABI-007
timeFrame: Up to 53 months
measure: The Number of Participants With at Least One Dose Delay for ABI-007
timeFrame: Up to 53 months
measure: The Number of Participants With a Dose Interruption of ABI-007
timeFrame: Up to 53 months
Secondary outcomes:
measure: Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response (i.e., Total Response) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)
timeFrame: Up to 43 months (until progressed)
measure: Kaplan Meier Estimate for Time to Disease Progression (TTP)
timeFrame: Up to 43 months (until progressed)
measure: Kaplan Meier Estimate for Duration of Response
timeFrame: Up to 43 months (until progressed)
measure: Kaplan Meier Estimate for Participant Survival
timeFrame: Up to 56 months
measure: Kaplan Meier Estimate for Progression-Free Survival (PFS)
timeFrame: up to 56 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Division of Hematology/Oncology University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: Little Rock Hematology Oncology Associates
state: Arkansas
city: Fresno
country: United States
facility: California Oncology of the Central Valley
state: California
city: Glendale
country: United States
facility: Glendale Memorial Hospital & Health Center
state: California
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Bridgeport
country: United States
facility: Oncology Associates of Bridgeport
state: Connecticut
city: Boynton Beach
country: United States
facility: Palm Beach Institute of Hematology and Oncology
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute/Breast Cancer Center
state: Florida
city: Hudson
country: United States
facility: Florida Cancer Institute
state: Florida
city: Lake Worth
country: United States
facility: Hematology Oncology Associates
state: Florida
city: Lake Worth
country: United States
facility: Medical Specialist of the Palm Beaches, Inc
state: Florida
city: Saint Petersburg
country: United States
facility: Gulfcoast Oncology Associates
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology & Oncology Associates
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, PC
state: Georgia
city: Stockbridge
country: United States
facility: Center of Hope for Cancers and Blood
state: Georgia
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine & Blood Disorders
state: Maine
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Harbor View Cancer Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center Moakley Building, Solomont Center for Hematology & Medical Oncology
state: Massachusetts
city: Peabody
country: United States
facility: North Shore Medical Cancer Center
state: Massachusetts
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Englewood
country: United States
facility: Drs. Forte, Schleidere, & Attas, PA
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Rosewell Park Cancer Institute Elm & Carlton Carlton Building
state: New York
city: New York
country: United States
facility: Beth Israel Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: NYU Clinical Cancer Center
state: New York
city: Washington
country: United States
facility: Marion L. Shepard Cancer Center
state: North Carolina
city: Canton
country: United States
facility: Medical Oncology Aultman Hospital
state: Ohio
city: Lawton
country: United States
facility: Cancer Centers of Southwest Oklahoma Research
state: Oklahoma
city: Willow Grove
country: United States
facility: Abington Hematology Oncology
state: Pennsylvania
city: Collierville
country: United States
facility: Family Cancer Center
state: Tennessee
city: Knoxville
country: United States
facility: Tennessee Cancer Specialists
state: Tennessee
city: Austin
country: United States
facility: TX Oncology, PA
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology & Hematology Clinical Research Dept.
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Oncology
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: San Juan
country: Puerto Rico
facility: Metropolitan Oncology Center
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Andrew Seidman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seidman AD, Conlin AK, Bach A, Moynahan ME, Lake D, Forero A, Wright GS, Hackney MH, Clawson A, Norton L, Hudis CA. Randomized phase II trial of weekly vs. every 2 weeks vs. every 3 weeks nanoparticle albumin-bound paclitaxel with bevacizumab as first-line chemotherapy for metastatic breast cancer. Clin Breast Cancer. 2013 Aug;13(4):239-246.e1. doi: 10.1016/j.clbc.2013.02.008.
citation: Conlin AK, Seidman AD, Bach A, Lake D, Dickler M, D'Andrea G, Traina T, Danso M, Brufsky AM, Saleh M, Clawson A, Hudis CA. Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. Clin Breast Cancer. 2010 Aug 1;10(4):281-7. doi: 10.3816/CBC.2010.n.036.