Weekly vs. Every 2 Week vs. Every 3 Week Administration of ABI-007 (Abraxane)/Bevacizumab Combination in Metastatic Breast Cancer

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.

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.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms; Neoplasm Metastasis
• Intervention / Treatment: Drug: ABI-007 (Abraxane); Drug: bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico
    • Metropolitan Oncology Center
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Division of Hematology/Oncology University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States
      • Little Rock Hematology Oncology Associates
  • California
    • Fresno, California, United States
      • California Oncology of the Central Valley
    • Glendale, California, United States
      • Glendale Memorial Hospital & Health Center
  • Colorado
    • Fort Collins, Colorado, United States
      • Front Range Cancer Specialists
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Oncology Associates of Bridgeport
  • Florida
    • Boynton Beach, Florida, United States
      • Palm Beach Institute of Hematology and Oncology
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute/Breast Cancer Center
    • Hudson, Florida, United States
      • Florida Cancer Institute
    • Lake Worth, Florida, United States
      • Hematology Oncology Associates
    • Lake Worth, Florida, United States
      • Medical Specialist of the Palm Beaches, Inc
    • Saint Petersburg, Florida, United States
      • Gulfcoast Oncology Associates
  • Georgia
    • Atlanta, Georgia, United States
      • Peachtree Hematology & Oncology Associates
    • Marietta, Georgia, United States
      • Northwest Georgia Oncology Centers, PC
    • Stockbridge, Georgia, United States, 30281
      • Center of Hope for Cancers and Blood
  • Maine
    • Scarborough, Maine, United States
      • Maine Center for Cancer Medicine & Blood Disorders
  • Maryland
    • Baltimore, Maryland, United States
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States
      • Harbor View Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Boston Medical Center Moakley Building, Solomont Center for Hematology & Medical Oncology
    • Peabody, Massachusetts, United States, 01960
      • North Shore Medical Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States
      • St. John's Mercy Medical Center
  • Nebraska
    • Omaha, Nebraska, United States
      • Nebraska Methodist Hospital
  • New Jersey
    • Englewood, New Jersey, United States
      • Drs. Forte, Schleidere, & Attas, PA
    • Livingston, New Jersey, United States
      • Saint Barnabas Medical Center
    • Long Branch, New Jersey, United States
      • Monmouth Medical Center
  • New York
    • Buffalo, New York, United States
      • Rosewell Park Cancer Institute Elm & Carlton Carlton Building
    • New York, New York, United States
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States
      • Nyu Clinical Cancer Center
    • New York, New York, United States
      • Beth Israel Comprehensive Cancer Center
  • North Carolina
    • Washington, North Carolina, United States
      • Marion L. Shepard Cancer Center
  • Ohio
    • Canton, Ohio, United States
      • Medical Oncology Aultman Hospital
  • Oklahoma
    • Lawton, Oklahoma, United States
      • Cancer Centers of Southwest Oklahoma Research
  • Pennsylvania
    • Willow Grove, Pennsylvania, United States
      • Abington Hematology Oncology
  • Tennessee
    • Collierville, Tennessee, United States
      • Family Cancer Center
    • Knoxville, Tennessee, United States
      • Tennessee Cancer Specialists
  • Texas
    • Austin, Texas, United States
      • TX Oncology, PA
    • San Antonio, Texas, United States
      • South Texas Oncology & Hematology Clinical Research Dept.
  • Virginia
    • Richmond, Virginia, United States
      • Virginia Commonwealth University Medical Oncology
  • Washington
    • Seattle, Washington, United States
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 260 mg/m^2 ABI-007 every 3 weeks; 260 mg/m^2 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks	Drug: ABI-007 (Abraxane); 30 minute infusions; Other Names: Abraxane; paclitaxel bound to albumin; Drug: bevacizumab; infusions; Other Names: Avastin
Experimental: 260 mg/m^2 ABI-007 every 2 weeks; 260 mg/m^2 ABI-007 every 2 weeks and 10 mg/kg bevacizumab every 2 weeks	Drug: ABI-007 (Abraxane); 30 minute infusions; Other Names: Abraxane; paclitaxel bound to albumin; Drug: bevacizumab; infusions; Other Names: Avastin
Experimental: 130 mg/m^2 ABI-007 weekly; 130 mg/m^2 ABI-007 weekly (without a week of 'rest') and 10 mg/kg bevacizumab every 2 weeks	Drug: ABI-007 (Abraxane); 30 minute infusions; Other Names: Abraxane; paclitaxel bound to albumin; Drug: bevacizumab; infusions; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants Confirmed Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)	Using the RECIST response criteria version 1.0, the percent of participants achieving either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.	Up to 43 months
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)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) ANC counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9L; Grade 2 = <1.5 - 1.0*10^9L; Grade 3 = <1.0 - 0.5*10^9L; Grade 4 = <0.5*10^9L	up to 54 months
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)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) WBC counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal -3.0*10^9/L; Grade 2 = <3.0 - 2.0*10^9/L; Grade 3 = <2.0 - 1.0*10^9/L; Grade 4 = <1.0*10^9/L	up to 54 months
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)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) platelet counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9/L; Grade 2 = <75.0 - 50.0*10^9/L; Grade 3 = <50.0 - 25.0*10^9/L; Grade 4 = <25.0*10^9/L	up to 54 months
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)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) hemoglobin levels were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 100g/L; Grade 2 = <100 - 80g/L; Grade 3 = <80 - 65g/L; Grade 4 = <65g/L	up to 54 months
The Number of Participants With at Least One Dose Reduction for ABI-007	Participants with at least one dose reduction for ABI-007. ABI-007 (Abraxane) dose could be reduced according to protocol guidelines if the participant was experiencing toxicities. Participants were allowed two ABI-007 (Abraxane) dose reductions during the course of the trial. This outcome is considered to be both a safety and an efficacy outcome.	Up to 53 months
The Number of Participants With at Least One Dose Delay for ABI-007	Participants with at least one dose delay for ABI-007. Treatment delays of no longer than 2 weeks allowed participants to recovery from acute toxicity. If treatment was delayed beyond 2 weeks, continuing treatment on protocol was at the physician's discretion, based upon the best interests of the participant. This outcome is considered to be both a safety and an efficacy outcome.	Up to 53 months
The Number of Participants With a Dose Interruption of ABI-007	Number of participants who interrupted (omitted) a dose at some point in the treatment period. This outcome is considered to be both a safety and an efficacy outcome.	Up to 53 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), the percentage of participants achieving either; A complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or; A partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions or; Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for progressive disease.	Up to 43 months (until progressed)
Kaplan Meier Estimate for Time to Disease Progression (TTP)	Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.	Up to 43 months (until progressed)
Kaplan Meier Estimate for Duration of Response	Duration of response was defined as the time from response to the time of disease progression for participants who achieve an objective confirmed complete (CR) or partial overall response (PR). Disease progression is based on the assessments by the investigator. Participants who did not have disease progression following a confirmed complete or partial target response were censored at the last known time that the participant was evaluated for response	Up to 43 months (until progressed)
Kaplan Meier Estimate for Participant Survival	Participant survival was summarized using Kaplan-Meier estimate of the time of first dose of study drug to the last known time that the participant was alive. Participants that were alive at the end of follow-up would be censored at the last known time that the patient was alive.	Up to 56 months
Kaplan Meier Estimate for Progression-Free Survival (PFS)	PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.	up to 56 months

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Principal Investigator: Andrew Seidman, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2006
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: January 24, 2006
• First Submitted That Met QC Criteria: January 24, 2006
• First Posted (Estimate): January 25, 2006

Study Record Updates

• Last Update Posted (Actual): November 22, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: First Line Metastatic Breast Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: CA023