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Paclitaxel With or Without Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
NCIC Clinical Trials Group
NSABP Foundation Inc
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00028990
First received: January 4, 2002
Last updated: March 8, 2012
Last verified: January 2010
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known whether paclitaxel works better with or without bevacizumab in treating breast cancer.

PURPOSE: This randomized phase III trial is to see if paclitaxel works better with or without bevacizumab in treating patients who have locally recurrent or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Tial Of Paclitaxel Versus Paclitaxel Plus Bevacizumab (rhuMAb VEGF) As First-Line Therapy For Locally Recurrent or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]

Enrollment: 722
Study Start Date: December 2001
Study Completion Date: May 2009
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Paclitaxel + Bevacizumab Drug: bevacizumab
10 mg/kg following paclitaxel treatment on weeks 1 and 3 of every 4-week cycle
Other Name: Avastin
Drug: Paclitaxel
90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest
Active Comparator: Paclitaxel Drug: Paclitaxel
90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest

Detailed Description:

OBJECTIVES:

  • Compare the time to treatment failure in patients with locally recurrent or metastatic breast cancer treated with paclitaxel with or without bevacizumab.
  • Compare the objective response rate, duration of response, overall survival, and time to progression in patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease-free interval (no more than 24 months vs more than 24 months), number of metastatic sites (less than 3 vs 3 or more), treatment with prior adjuvant chemotherapy (yes vs no), and estrogen receptor status (positive vs negative vs unknown). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 followed by bevacizumab IV over 30-90 minutes on days 1 and 15.
  • Arm II: Patients receive paclitaxel as in arm I. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and on day 1 of weeks 17 and 33.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 316-650 patients (158-325 per treatment arm) will be accrued for this study within 31 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the breast
  • Locally recurrent disease that is not amenable to surgical resection with curative intent OR
  • Metastatic disease
  • No HER-2-overexpressing (3+) breast cancer unless previously treated with trastuzumab (Herceptin)

    • Unknown HER-2 status allowed provided herceptin-based therapy inappropriate or not indicated
  • No prior or radiologic evidence of CNS metastases, including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Male or female

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No prior bleeding diathesis

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • SGOT no greater than 2 times upper limit of normal (ULN) (5 times ULN for known liver involvement)
  • PT/PTT no greater than 1.5 times normal
  • INR no greater than 1.5 times normal

Renal:

  • Creatinine no greater than 2.0 mg/dL
  • No proteinuria by dipstick urinalysis
  • Trace proteinuria allowed
  • Proteinuria less than 500 mg by 24-hour urine collection if proteinuria at least 1+ by urinalysis

Cardiovascular:

  • No clinically significant cardiovascular disease
  • No myocardial infarction within the past 12 months
  • No unstable angina
  • No prior deep vein thrombosis
  • No grade 2 or greater peripheral vascular disease
  • No uncontrolled congestive heart failure
  • No uncontrolled hypertension (systolic blood pressure greater than 170 mmHg and diastolic blood pressure greater than 95 mm Hg)
  • No prior cerebrovascular accident

Pulmonary:

  • No prior pulmonary embolism

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective non-hormonal contraception
  • No history of seizures
  • No non-healing wound or fracture
  • No hypersensitivity to paclitaxel, Cremophor EL, Chinese hamster ovary cell products, or other recombinant human antibodies
  • No active infection requiring parenteral antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics

Chemotherapy:

  • No prior chemotherapy for locally recurrent or metastatic breast cancer
  • At least 12 months since prior adjuvant or neoadjuvant taxane therapy
  • At least 3 weeks since prior adjuvant chemotherapy

Endocrine therapy:

  • At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic breast cancer

Radiotherapy:

  • At least 3 weeks since prior radiotherapy
  • No prior radiotherapy to only site of disease
  • No concurrent local radiotherapy for pain control or life-threatening situations (e.g, superior vena cava syndrome, spinal cord compression, or CNS metastases)

Surgery:

  • At least 4 weeks since prior major surgical procedure except placement of vascular access device or breast biopsy
  • At least 7 days since prior minor surgical procedure, including placement of an access device or fine needle aspiration

Other:

  • At least 10 days since prior anticoagulant therapy (low-dose anticoagulant therapy to maintain patency of a vascular access device allowed)
  • At least 10 days since prior and no concurrent daily aspirin (more than 325 mg/day) or other non-steroidal anti-inflammatory medication known to inhibit platelet function
  • No concurrent dipyridamole, ticlopidine, clopidogrel, or cilostazol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028990

  Hide Study Locations
Locations
United States, Alabama
MBCCOP - Gulf Coast
Mobile, Alabama, United States, 36607
United States, Arizona
CCOP - Mayo Clinic Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342-1701
United States, Illinois
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
Siouxland Hematology-Oncology
Sioux City, Iowa, United States, 51101-1733
United States, Louisiana
CCOP - Ochsner
New Orleans, Louisiana, United States, 70121
United States, Michigan
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CentraCare Health Plaza
Saint Cloud, Minnesota, United States, 56303
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Dakota
Medcenter One Health System
Bismarck, North Dakota, United States, 58501-5505
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Altru Cancer Center
Grand Forks, North Dakota, United States, 58201
United States, Ohio
CCOP - Dayton
Dayton, Ohio, United States, 45429
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
United States, Oklahoma
CCOP - Oklahoma
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212-4772
United States, South Carolina
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Sponsors and Collaborators
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
NCIC Clinical Trials Group
NSABP Foundation Inc
Investigators
Study Chair: Kathy Miller, MD Indiana University Melvin and Bren Simon Cancer Center
Investigator: Robin Zon, MD Elkhart General Hospital
Study Chair: Edith A. Perez, MD Mayo Clinic
Study Chair: Tamara N. Shenkier, MD British Columbia Cancer Agency
Study Chair: Melody A. Cobleigh, MD Rush University Medical Center
  More Information

Additional Information:
Publications:
Wagner LI, Wang M, Miller K, et al.: Health-related quality of life among patients with metastatic breast cancer receiving paclitaxel versus paclitaxel plus bevacizumab: results from the Eastern Cooperative Oncology Group (ECOG) study E2100. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-5078, S239, 2006.
Miller KD, Wang M, Gralow J, et al.: A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-3, 2005.
Gray R, Giantonio BJ, O'Dwyer PJ, et al.: The safety of adding angiogenesis inhibition into treatment for colorectal, breast, and lung cancer: the Eastern Cooperative Oncology Group's (ECOG) experience with bevacizumab (anti-VEGF). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-825, 2003.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00028990     History of Changes
Other Study ID Numbers: CDR0000069156, E2100, NCCTG-E2100, CAN-NCIC-MAC3, NSABP-E2100
Study First Received: January 4, 2002
Last Updated: March 8, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
stage IV breast cancer
recurrent breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 27, 2014