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

NCT ID: NCT00028990

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 722 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-29
• Study Completion Date: 2009-05-31

Brief Summary

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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paclitaxel + Bevacizumab

Group Type: ACTIVE_COMPARATOR

bevacizumab

Intervention Type: DRUG

10 mg/kg following paclitaxel treatment on weeks 1 and 3 of every 4-week cycle

Paclitaxel

Intervention Type: DRUG

90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest

Paclitaxel

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest

Interventions

bevacizumab

10 mg/kg following paclitaxel treatment on weeks 1 and 3 of every 4-week cycle

Intervention Type: DRUG

Paclitaxel

90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathy Miller, MD

Role: STUDY_CHAIR

Indiana University Melvin and Bren Simon Cancer Center

Robin Zon, MD

Role:

Elkhart General Hospital

Edith A. Perez, MD

Role: STUDY_CHAIR

Mayo Clinic

Tamara N. Shenkier, MD

Role: STUDY_CHAIR

British Columbia Cancer Agency

Melody A. Cobleigh, MD

Role: STUDY_CHAIR

Rush University Medical Center

Locations

MBCCOP - Gulf Coast

Mobile, Alabama, United States

CCOP - Mayo Clinic Scottsdale Oncology Program

Scottsdale, Arizona, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

CCOP - Atlanta Regional

Atlanta, Georgia, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

CCOP - Duluth

Duluth, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CentraCare Health Plaza

Saint Cloud, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Medcenter One Health System

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Altru Cancer Center

Grand Forks, North Dakota, United States

CCOP - Dayton

Dayton, Ohio, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

CCOP - Oklahoma

Tulsa, Oklahoma, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD; ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008 Oct 1;26(28):4672-8. doi: 10.1200/JCO.2008.16.1612.

Reference Type: RESULT

PMID: 18824714 (View on PubMed)

Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. doi: 10.1056/NEJMoa072113.

Reference Type: RESULT

PMID: 18160686 (View on PubMed)

Cella D, Wang M, Wagner L, Miller K. Survival-adjusted health-related quality of life (HRQL) among patients with metastatic breast cancer receiving paclitaxel plus bevacizumab versus paclitaxel alone: results from Eastern Cooperative Oncology Group Study 2100 (E2100). Breast Cancer Res Treat. 2011 Dec;130(3):855-61. doi: 10.1007/s10549-011-1725-6. Epub 2011 Aug 27.

Reference Type: RESULT

PMID: 21874312 (View on PubMed)

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.

Reference Type: RESULT

Miller KD. E2100: a phase III trial of paclitaxel versus paclitaxel/bevacizumab for metastatic breast cancer. Clin Breast Cancer. 2003 Feb;3(6):421-2. doi: 10.3816/CBC.2003.n.007. No abstract available.

Reference Type: RESULT

PMID: 12636887 (View on PubMed)

Other Identifiers

E2100

Identifier Type: -

Identifier Source: secondary_id

NCCTG-E2100

Identifier Type: -

Identifier Source: secondary_id

CAN-NCIC-MAC3

Identifier Type: -

Identifier Source: secondary_id

NSABP-E2100

Identifier Type: -

Identifier Source: secondary_id

CDR0000069156

Identifier Type: -

Identifier Source: org_study_id