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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028990
• Other study ID #: CDR0000069156
• Secondary ID: E2100NCCTG-E2100
• Status: Completed
• Phase: Phase 3
• Start date: January 29, 2002
• Est. completion date: May 2009

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 722
• Est. completion date: May 2009
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• bevacizumab
10 mg/kg following paclitaxel treatment on weeks 1 and 3 of every 4-week cycle
• Paclitaxel
90 mg/m2 IV infusion over 1 hour every week for 3 weeks followed by 1 week rest

Locations

Country	Name	City	State
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Medcenter One Health System	Bismarck	North Dakota
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Rapid City Regional Hospital	Rapid City	South Dakota
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 - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois

Sponsors (5)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI), NCIC Clinical Trials Group, North Central Cancer Treatment Group, NSABP Foundation Inc

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (6)

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 — View Citation

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.

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. — View Citation

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 (E210

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. — View Citation

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 endo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival		Assessed every 3 months for 2 years, then every 6 months for 3 years