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

NCT00281528 | Terminated Phase 2 Results

• 1 other identifier: CA023
• Study Type: interventional
• Target: 208
• Locations: 2 countries
• Sites: 40

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.

Conditions

Breast Neoplasms; Neoplasm Metastasis

Keywords

First Line Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (5)

• 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)

  Up to 43 months (until progressed)

• Kaplan Meier Estimate for Time to Disease Progression (TTP)

  Up to 43 months (until progressed)

• Kaplan Meier Estimate for Duration of Response

  Up to 43 months (until progressed)

• Kaplan Meier Estimate for Participant Survival

  Up to 56 months

• Kaplan Meier Estimate for Progression-Free Survival (PFS)

  up to 56 months

Study Arms (3)

260 mg/m^2 ABI-007 every 3 weeks

EXPERIMENTAL

260 mg/m\^2 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks

Drug: ABI-007 (Abraxane); Drug: bevacizumab

260 mg/m^2 ABI-007 every 2 weeks

EXPERIMENTAL

260 mg/m\^2 ABI-007 every 2 weeks and 10 mg/kg bevacizumab every 2 weeks

Drug: ABI-007 (Abraxane); Drug: bevacizumab

130 mg/m^2 ABI-007 weekly

EXPERIMENTAL

130 mg/m\^2 ABI-007 weekly (without a week of 'rest') and 10 mg/kg bevacizumab every 2 weeks

Drug: ABI-007 (Abraxane); Drug: bevacizumab

Interventions

ABI-007 (Abraxane) DRUG

30 minute infusions

Also known as: Abraxane, paclitaxel bound to albumin

130 mg/m^2 ABI-007 weekly; 260 mg/m^2 ABI-007 every 2 weeks; 260 mg/m^2 ABI-007 every 3 weeks

bevacizumab DRUG

infusions

Also known as: Avastin

130 mg/m^2 ABI-007 weekly; 260 mg/m^2 ABI-007 every 2 weeks; 260 mg/m^2 ABI-007 every 3 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (40)

Division of Hematology/Oncology University of Alabama at Birmingham

Birmingham, Alabama, United States

Location

Little Rock Hematology Oncology Associates

Little Rock, Arkansas, United States

Location

California Oncology of the Central Valley

Fresno, California, United States

Location

Glendale Memorial Hospital & Health Center

Glendale, California, United States

Location

Front Range Cancer Specialists

Fort Collins, Colorado, United States

Location

Oncology Associates of Bridgeport

Bridgeport, Connecticut, 06610, United States

Location

Palm Beach Institute of Hematology and Oncology

Boynton Beach, Florida, United States

Location

Memorial Cancer Institute/Breast Cancer Center

Hollywood, Florida, 33021, United States

Location

Florida Cancer Institute

Hudson, Florida, United States

Location

Hematology Oncology Associates

Lake Worth, Florida, United States

Location

Medical Specialist of the Palm Beaches, Inc

Lake Worth, Florida, United States

Location

Gulfcoast Oncology Associates

St. Petersburg, Florida, United States

Location

Peachtree Hematology & Oncology Associates

Atlanta, Georgia, United States

Location

Northwest Georgia Oncology Centers, PC

Marietta, Georgia, United States

Location

Center of Hope for Cancers and Blood

Stockbridge, Georgia, 30281, United States

Location

Maine Center for Cancer Medicine & Blood Disorders

Scarborough, Maine, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Location

Harbor View Cancer Center

Baltimore, Maryland, United States

Location

Boston Medical Center Moakley Building, Solomont Center for Hematology & Medical Oncology

Boston, Massachusetts, United States

Location

North Shore Medical Cancer Center

Peabody, Massachusetts, 01960, United States

Location

St. John's Mercy Medical Center

St Louis, Missouri, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Location

Drs. Forte, Schleidere, & Attas, PA

Englewood, New Jersey, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, United States

Location

Rosewell Park Cancer Institute Elm & Carlton Carlton Building

Buffalo, New York, United States

Location

Beth Israel Comprehensive Cancer Center

New York, New York, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Location

NYU Clinical Cancer Center

New York, New York, United States

Location

Marion L. Shepard Cancer Center

Washington, North Carolina, United States

Location

Medical Oncology Aultman Hospital

Canton, Ohio, United States

Location

Cancer Centers of Southwest Oklahoma Research

Lawton, Oklahoma, United States

Location

Abington Hematology Oncology

Willow Grove, Pennsylvania, United States

Location

Family Cancer Center

Collierville, Tennessee, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Location

TX Oncology, PA

Austin, Texas, United States

Location

South Texas Oncology & Hematology Clinical Research Dept.

San Antonio, Texas, United States

Location

Virginia Commonwealth University Medical Oncology

Richmond, Virginia, United States

Location

Swedish Cancer Institute

Seattle, Washington, United States

Location

Metropolitan Oncology Center

San Juan, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 23829890 BACKGROUND

• 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.

  PMID: 20705560 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Albumin-Bound Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Andrew Seidman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2006
• First Posted: January 25, 2006
• Study Start: February 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: March 1, 2011
• Last Updated: November 22, 2019
• Results First Posted: March 13, 2012

Record last verified: 2019-11

Locations

US (39); PR (1)