Paclitaxel With or Without Trastuzumab in Treating Women With Inoperable, Recurrent, or Metastatic Breast Cancer With or Without Overexpression of HER2/Neu - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003440

Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known which of two regimens of paclitaxel, with or without trastuzumab, is more effective in treating women with inoperable, recurrent, or metastatic breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of paclitaxel, with or without trastuzumab, in treating women who have breast cancer that is inoperable, recurrent, or metastatic, with or without overexpression of HER2/neu.

Condition	Intervention	Phase
Breast Cancer	Biological: trastuzumab Drug: paclitaxel	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase III Study of Paclitaxel Via Weekly One Hour Infusion Versus Standard Three Hour Infusion Every Three Weeks in the Treatment of Patients With Metastatic Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel Trastuzumab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	580
Study Start Date:	July 1998
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the response rate in women with inoperable, recurrent, or metastatic breast cancer treated with paclitaxel via one-hour infusion every week vs 3-hour infusion every 3 weeks, regardless of HER2/neu status and assignment to trastuzumab (Herceptin®).
Compare the response rate and quality of life of patients with HER2/neu-nonoverexpressing disease treated with 1 of these 2 paclitaxel regimens with or without trastuzumab.
Correlate amplification and overexpression of the growth factor receptor ErbB2 by immunohistochemistry and fluorescent in situ hybridization (FISH) with response rate, time to progression, and overall survival of patients treated with these regimens.
Correlate ErbB2 shed extracellular domain (ECD) with response rate, time to progression, and overall survival of patients treated with these regimens.
Assess the patterns of ErbB2/ECD after treatment with these regimens and upon relapse in these patients.
Compare the time to progression and survival of patients with HER2/neu-overexpressing disease treated with these regimens.
Compare the time to progression and survival of patients with HER2/neu-nonoverexpressing disease treated with these regimens.
Compare the cardiac toxicity of these regimens as measured by changes in left ventricular ejection fraction from baseline to follow-up measurements in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy for metastatic disease (none or recurrence more than 6 months after adjuvant therapy vs one or none but recurrence less than 6 months after adjuvant therapy) and HER2/neu overexpression (yes vs no). Patients are assigned to 1 of 2 treatment groups based on HER2/neu status.

Group A (HER2/neu-nonoverexpressing): Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive paclitaxel IV over 3 hours on day 1.
- Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
- Arm III: Patients receive paclitaxel as in arm I. Patients receive an initial loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 of course 1 and maintenance dose of trastuzumab IV over 30 minutes on day 1 of subsequent courses and on days 8 and 15 of all courses. Trastuzumab is administered immediately after completion of paclitaxel infusion on weeks of concurrent administration.
- Arm IV: Patients receive paclitaxel as in arm II and trastuzumab as in arm III.
Group B: (HER2/neu-overexpressing): Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive treatment as in arm III (group A).
- Arm II: Patients receive treatment as in arm IV (group A). In both groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at 3, 6, and 9 months.

Patients are followed at 6, 12, and 18 months and then annually for 5 years or until death.

PROJECTED ACCRUAL: A total of 580 patients will be accrued for this study within 3 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically proven inoperable, recurrent, or metastatic adenocarcinoma of the breast
Known HER2/neu status
Measurable disease
No CNS metastases unless at least 6 months since prior cranial radiotherapy and the patient is asymptomatic and not receiving corticosteroids for this condition at time of enrollment
No leptomeningeal carcinoma (carcinomatous meningitis)
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Sex:

Female

Menopausal status:

Not specified

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin normal
SGOT no greater than 3 times upper limit of normal

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

Left ventricular ejection fraction at least 45%

Other:

Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior trastuzumab (Herceptin®)
Concurrent epoetin alfa allowed

Chemotherapy:

No more than 1 prior chemotherapy regimen for locally advanced or metastatic breast cancer
No prior taxane for locally advanced or metastatic breast cancer
No more than 1 prior adjuvant chemotherapy regimen
At least 12 months since prior adjuvant taxane and recovered
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, melphalan, or mitomycin)
No other concurrent chemotherapy

Endocrine therapy:

See Disease Characteristics
More than 4 weeks since prior hormonal therapy
More than 1 week since prior hormonal therapy if documented tumor progression
No concurrent hormonal therapy except any of the following:
- Steroids for documented CNS metastases, adrenal failure, septic shock, or prevention of serious allergic reaction or emesis
- Hormonal therapy for nonmalignant conditions (e.g., insulin for diabetes)

Radiotherapy:

See Disease Characteristics
No concurrent radiotherapy except whole brain irradiation for CNS disease

Surgery:

More than 2 weeks since prior surgery, other than biopsy or placement of venous access device

Other:

Concurrent bisphosphonate (e.g., pamidronate) therapy allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003440

Hide Study Locations

Locations

United States, Alabama
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
United States, California
California Cancer Center
Fresno, California, United States, 93720
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
Howard University Cancer Center
Washington, District of Columbia, United States, 20060
Veterans Affairs Medical Center - Washington, DC
Washington, District of Columbia, United States, 20422
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307-5000
United States, Florida
Broward General Medical Center
Fort Lauderdale, Florida, United States, 33316
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center
West Palm Beach, Florida, United States, 33401
Memorial Regional Hospital Comprehensive Cancer Center
Hollywood, Florida, United States, 33021
United States, Illinois
Louis A. Weiss Memorial Hospital
Chicago, Illinois, United States, 60640
Saint Anthony Medical Center
Rockford, Illinois, United States, 61108
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
West Suburban Center for Cancer Care
River Forest, Illinois, United States, 60305
United States, Indiana
Fort Wayne Medical Oncology and Hematology, Incorporated
Fort Wayne, Indiana, United States, 46885-5099
United States, Iowa
Hematology Oncology Associates of the Quad Cities
Bettendorf, Iowa, United States, 52722
Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242-1009
United States, Kentucky
Baptist Hospital East - Louisville
Louisville, Kentucky, United States, 40207
United States, Maryland
Marlene and Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
Veterans Affairs Medical Center - Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
University of Massachusetts Memorial Medical Center - University Campus
Worcester, Massachusetts, United States, 01655
United States, Michigan
Lakeland Medical Center - St. Joseph
Saint Joseph, Michigan, United States, 49085
United States, Minnesota
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
Veterans Affairs Medical Center - Columbia (Truman Memorial)
Columbia, Missouri, United States, 65201
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
Veterans Affairs Medical Center - Las Vegas
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
United States, New York
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
Syracuse, New York, United States, 13217
Elmhurst Hospital Center
Elmhurst, New York, United States, 11373
Queens Cancer Center of Queens Hospital
Jamaica, New York, United States, 11432
Mount Sinai Medical Center, NY
New York, New York, United States, 10029
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
North Shore University Hospital
Manhasset, New York, United States, 11030
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
Cape Fear Valley Health System
Fayetteville, North Carolina, United States, 28302-2000
FirstHealth Moore Regional Hospital
Pinehurst, North Carolina, United States, 28374
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
CCOP - Southeast Cancer Control Consortium
Winston-Salem, North Carolina, United States, 27104-4241
Lenoir Memorial Hospital Cancer Center
Kinston, North Carolina, United States, 28503-1678
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, United States, 27599-7295
New Hanover Regional Medical Center
Wilmington, North Carolina, United States, 28402-9025
NorthEast Oncology Associates
Concord, North Carolina, United States, 28025
Veterans Affairs Medical Center - Asheville
Asheville, North Carolina, United States, 28805
Veterans Affairs Medical Center - Durham
Durham, North Carolina, United States, 27705
United States, North Dakota
Veterans Affairs Medical Center - Fargo
Fargo, North Dakota, United States, 58102
United States, Rhode Island
Lifespan: The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Texas
Veterans Affairs Medical Center - Dallas
Dallas, Texas, United States, 75216
United States, Vermont
Vermont Cancer Center
Burlington, Vermont, United States, 05401-3498
Veterans Affairs Medical Center - White River Junction
White River Junction, Vermont, United States, 05009
United States, Virginia
Martha Jefferson Hospital
Charlottesville, Virginia, United States, 22902
MBCCOP - Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Oncology and Hematology Associates of Southwest Virginia, Inc.
Roanoke, Virginia, United States, 24014
Virginia Oncology Associates - Norfolk
Norfolk, Virginia, United States, 23502
United States, West Virginia
St. Mary's Medical Center
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Ministry Medical Group - Northern Region
Rhinelander, Wisconsin, United States, 54501
Puerto Rico
University of Puerto Rico School of Medicine Medical Sciences Campus
San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Andrew D. Seidman, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Rimm DL, Broadwater G, Friedman P, et al.: Uniformly positive (>80%) HER2 expression maximizes sensitivity and specificity for prediction of response to trastuzumab in CALGB 9840. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-6046, 2008.

Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9.

Naughton MJ, Gu L, Wang XF, et al.: Quality of life (QOL) companion to CALGB 9840: a phase III study of paclitaxel (P) via weekly 1 hour (hr) versus standard 3 hour infusion every 3 weeks with trastuzumab in the treatment of patients with/without HER-2/neu-overexpressing metastatic breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-674, 2006.

Seidman AD, Broadwater G, Carney W, et al.: Serum HER2 extracellular domain (ECD) levels and efficacy of weekly (W) or every 3-weekly (q3W) paclitaxel (P) with or without trastuzumab (T) in patients (pts) with metastatic breast cancer (MBC): CALGB 150002/9840. [Abstract] J Clin Oncol 23 (Suppl 16): A-558, 18s, 2005.

Seidman AD, Berry D, Cirrincione C, et al.: CALGB 9840: phase III study of weekly (W) paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC. [Abstract] J Clin Oncol 22 (Suppl 14): A-512, 6s, 2004.

Polite BN, Cirrincione C, Fleming GF, Berry DA, Seidman A, Muss H, Norton L, Shapiro C, Bakri K, Marcom K, Lake D, Schwartz JH, Hudis C, Winer EP. Racial differences in clinical outcomes from metastatic breast cancer: a pooled analysis of CALGB 9342 and 9840--Cancer and Leukemia Group B. J Clin Oncol. 2008 Jun 1;26(16):2659-65.

Kaufman PA, Broadwater G, Lezon-Geyda K, et al.: CALGB 150002: correlation of HER2 and chromosome 17 (ch17) copy number with trastuzumab (T) efficacy in CALGB 9840, paclitaxel (P) with or without T in HER2+ and HER2- metastatic breast cancer (MBC). [Abstract] J Clin Oncol 25 (Suppl 18): A-1009, 2007.

Polite BN, Cirrincione C, Fleming GF, et al.: Understanding racial differences in outcome from metastatic breast cancer (MBC): a pooled analysis of Cancer and Leukemia Group B (CALGB) 9342 and 9840. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-3097, 2005.

Study ID Numbers:	CDR0000066468, CLB-9840
Study First Received:	November 1, 1999
Last Updated:	June 6, 2009
ClinicalTrials.gov Identifier:	NCT00003440 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV breast cancer
recurrent breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:

Skin Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Breast Neoplasms
Antimitotic Agents
Pharmacologic Actions
Neoplasms

Neoplasms by Site
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Trastuzumab
Antineoplastic Agents, Phytogenic
Breast Diseases

ClinicalTrials.gov processed this record on November 25, 2009