Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI ECOG-2100 NCCTG-E2100, CAN-NCIC-MAC3, NSABP-E2100, E2100, NCT00028990, MAC3

Special Category: CTSU trial

Objectives

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

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

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.

Schneider BP, Wang M, Radovich M, et al.: 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 26 (28): 4672-8, 2008.[PUBMED Abstract]

Miller K, Wang M, Gralow J, et al.: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357 (26): 2666-76, 2007.[PUBMED Abstract]

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.

Miller KD: E2100: a phase III trial of paclitaxel versus paclitaxel/bevacizumab for metastatic breast cancer. Clin Breast Cancer 3 (6): 421-2, 2003.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Kathy Miller, MD, Protocol chair		Ph: 317-274-1690; 888-600-4822 Email: kathmill@iupui.edu
Robin Zon, MD, Protocol co-chair		Ph: 574-296-6536

North Central Cancer Treatment Group

Edith Perez, MD, Protocol chair		Ph: 904-953-7283 Email: perez.edith@mayo.edu

NCIC-Clinical Trials Group

Tamara Shenkier, MD, Protocol chair		Ph: 604-877-6000; 800-663-3333 Email: tshenkier@bccancer.bc.ca

National Surgical Adjuvant Breast and Bowel Project

Melody Cobleigh, MD, Protocol chair		Ph: 312-942-2242

Registry Information
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
Trial Start Date		2001-12-21
Registered in ClinicalTrials.gov		NCT00028990
Date Submitted to PDQ		2001-11-21
Information Last Verified		2006-07-27
NCI Grant/Contract Number		CA21115