Capecitabine, Vinorelbine, and Trastuzumab in Treating Patients With Metastatic Breast Cancer

NCT ID: NCT00093808

Last Updated: 2017-03-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-08-31

Study Completion Date

2013-05-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as capecitabine and vinorelbine, work in 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. Giving capecitabine and vinorelbine together with trastuzumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving capecitabine and vinorelbine together with trastuzumab works in treating patients who have metastatic breast cancer.

Detailed Description

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OBJECTIVES:

Primary

* Determine the overall response rate in patients with HER2/neu-overexpressing metastatic breast cancer treated with first- or second-line therapy comprising capecitabine, vinorelbine, and trastuzumab (Herceptin\^®).

Secondary

* Determine the time to disease progression, duration of response, and overall survival of patients treated with this regimen.
* Determine the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14, vinorelbine IV over 6-10 minutes on days 1 and 8, and trastuzumab (Herceptin\^®) IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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capecitabine + vinorelbine + trastuzumab

Patients receive oral capecitabine twice daily on days 1-14, vinorelbine IV over 6-10 minutes on days 1 and 8, and trastuzumab (Herceptin\^®) IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Group Type EXPERIMENTAL

trastuzumab

Intervention Type BIOLOGICAL

capecitabine

Intervention Type DRUG

vinorelbine tartrate

Intervention Type DRUG

Interventions

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trastuzumab

Intervention Type BIOLOGICAL

capecitabine

Intervention Type DRUG

vinorelbine tartrate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed invasive breast cancer

* Metastatic disease
* HER2/neu-positive by immunohistochemistry (3+ by HercepTest\^™ or equivalent) OR positive for amplification by fluorescent in situ hybridization

* Testing may be performed in the primary tumor or the metastatic site
* Received prior anthracycline or taxane as adjuvant therapy or for metastatic disease
* Measurable disease

* At least one measurable lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan
* The following are considered non-measurable disease:

* Bone lesions
* Leptomeningeal disease
* Ascites
* Pleural/pericardial effusion
* Inflammatory breast disease
* Lymphangitis cutis/pulmonis
* Abdominal masses that are not confirmed and followed by imaging techniques
* Cystic lesions
* No bone metastases as the only evidence of metastasis
* Previously treated CNS metastases allowed provided disease has been stable for ≥ the past 3 months
* Hormone receptor status:

* Not specified

PATIENT CHARACTERISTICS:

Age

* 18 and over

Sex

* Female or male

Performance status

* ECOG 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Hemoglobin ≥ 8.0 g/dL
* Platelet count ≥ 100,000/mm\^3
* No known uncontrolled coagulopathy

Hepatic

* Bilirubin ≤ 3.0 times the upper limit of normal (ULN)
* One of the following must be true:

* AST or ALT ≤ 5 times ULN AND alkaline phosphatase normal
* Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal
* Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
* INR ≤ 1.5 times ULN

Renal

* Calcium ≤ 11.5 mg/dL
* Creatinine ≤ 1.5 times ULN
* Creatinine clearance ≥ 30 mL/min

Cardiovascular

* LVEF ≥ 50% by MUGA or echocardiogram
* No clinically significant (i.e., active) cardiac disease
* No congestive heart failure
* No symptomatic coronary artery disease
* No myocardial infarction within the past 12 months
* No cardiac arrhythmia not controlled with medication

Gastrointestinal

* Able to take oral medication
* No lack of physical integrity of the upper gastrointestinal tract
* No clinically significant malabsorption syndrome

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 30 days after study participation
* No history of allergy or hypersensitivity to study drugs, drug product excipients, including polysorbate 80, or chemically similar agents
* No prior unanticipated severe reaction to fluoropyrimidine therapy
* No know hypersensitivity to fluorouracil
* No known dihydropyrimidine dehydrogenase deficiency
* No history of uncontrolled seizures or CNS disorders
* No clinically significant psychiatric disability that would preclude giving informed consent or study compliance
* No other serious uncontrolled infection or disease
* No other malignancy within the past 5 years except cured basal cell skin cancer, carcinoma in situ of the cervix, or contralateral breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Prior adjuvant trastuzumab (Herceptin\^®) allowed as adjuvant or first-line therapy for metastatic disease
* No concurrent immunotherapy

Chemotherapy

* See Disease Characteristics
* No more than 1 prior chemotherapy regimen in the advanced or metastatic (non-adjuvant) setting
* No prior continuous (≥ 24 hours) fluorouracil infusion
* No prior capecitabine
* No prior oral fluoropyrimidines (e.g., eniluracil and fluorouracil, uracil and tegafur, S1, or emitefur)

Endocrine therapy

* At least 1 day since prior hormonal therapy
* No concurrent hormonal therapy

Radiotherapy

* More than 4 weeks since prior radiotherapy to the axial skeleton (i.e., skull, spinal column, sternum, or ribs)
* No concurrent radiotherapy

Surgery

* More than 4 weeks since prior major surgery
* No prior organ allografts requiring immunosuppressive therapy

Other

* More than 4 weeks since prior investigational drugs
* No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
* No concurrent allopurinol, metronidazole, or cimetidine
* No other concurrent cytotoxic agents
* No other concurrent investigational drugs
* No other concurrent anticancer therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Winston Tan, MD, FACP

Role: STUDY_CHAIR

Mayo Clinic

Locations

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Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Rush-Copley Cancer Care Center

Aurora, Illinois, United States

Site Status

St. Joseph Medical Center

Bloomington, Illinois, United States

Site Status

Graham Hospital

Canton, Illinois, United States

Site Status

Memorial Hospital

Carthage, Illinois, United States

Site Status

Eureka Community Hospital

Eureka, Illinois, United States

Site Status

Galesburg Clinic, PC

Galesburg, Illinois, United States

Site Status

Galesburg Cottage Hospital

Galesburg, Illinois, United States

Site Status

Mason District Hospital

Havana, Illinois, United States

Site Status

Hopedale Medical Complex

Hopedale, Illinois, United States

Site Status

Joliet Oncology-Hematology Associates, Limited - West

Joliet, Illinois, United States

Site Status

McDonough District Hospital

Macomb, Illinois, United States

Site Status

Trinity Cancer Center at Trinity Medical Center - 7th Street Campus

Moline, Illinois, United States

Site Status

Moline, Illinois, United States

Site Status

BroMenn Regional Medical Center

Normal, Illinois, United States

Site Status

Community Cancer Center

Normal, Illinois, United States

Site Status

Community Hospital of Ottawa

Ottawa, Illinois, United States

Site Status

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, United States

Site Status

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, United States

Site Status

Proctor Hospital

Peoria, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

OSF St. Francis Medical Center

Peoria, Illinois, United States

Site Status

Illinois Valley Community Hospital

Peru, Illinois, United States

Site Status

Perry Memorial Hospital

Princeton, Illinois, United States

Site Status

St. Margaret's Hospital

Spring Valley, Illinois, United States

Site Status

Carle Cancer Center at Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

Elkhart General Hospital

Elkhart, Indiana, United States

Site Status

Howard Community Hospital

Kokomo, Indiana, United States

Site Status

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, United States

Site Status

Saint Anthony Memorial Health Centers

Michigan City, Indiana, United States

Site Status

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Site Status

Memorial Hospital of South Bend

South Bend, Indiana, United States

Site Status

Saint Joseph Regional Medical Center

South Bend, Indiana, United States

Site Status

McFarland Clinic, PC

Ames, Iowa, United States

Site Status

Bettendorf, Iowa, United States

Site Status

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, United States

Site Status

Mercy Capitol Hospital

Des Moines, Iowa, United States

Site Status

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Site Status

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, United States

Site Status

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, United States

Site Status

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, United States

Site Status

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

Site Status

John Stoddard Cancer Center at Iowa Lutheran Hospital

Des Moines, Iowa, United States

Site Status

Mercy Cancer Center at Mercy Medical Center - North Iowa

Mason City, Iowa, United States

Site Status

McCreery Cancer Center at Ottumwa Regional

Ottumwa, Iowa, United States

Site Status

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States

Site Status

Mercy Medical Center - Sioux City

Sioux City, Iowa, United States

Site Status

St. Luke's Regional Medical Center

Sioux City, Iowa, United States

Site Status

Hickman Cancer Center at Bixby Medical Center

Adrian, Michigan, United States

Site Status

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States

Site Status

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Site Status

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Site Status

Green Bay Oncology, Limited - Escanaba

Escanaba, Michigan, United States

Site Status

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

Dickinson County Healthcare System

Iron Mountain, Michigan, United States

Site Status

Foote Memorial Hospital

Jackson, Michigan, United States

Site Status

Haematology-Oncology Associates of Ohio and Michigan, PC

Lambertville, Michigan, United States

Site Status

Sparrow Regional Cancer Center

Lansing, Michigan, United States

Site Status

St. Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Community Cancer Center of Monroe

Monroe, Michigan, United States

Site Status

Mercy Memorial Hospital - Monroe

Monroe, Michigan, United States

Site Status

St. Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, United States

Site Status

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, United States

Site Status

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, United States

Site Status

St. John Macomb Hospital

Warren, Michigan, United States

Site Status

Alexandria, Minnesota, United States

Site Status

MeritCare Bemidji

Bemidji, Minnesota, United States

Site Status

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Site Status

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Duluth Clinic Cancer Center - Duluth

Duluth, Minnesota, United States

Site Status

CCOP - Duluth

Duluth, Minnesota, United States

Site Status

Miller - Dwan Medical Center

Duluth, Minnesota, United States

Site Status

Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status

Fergus Falls, Minnesota, United States

Site Status

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States

Site Status

Hutchinson Area Health Care

Hutchinson, Minnesota, United States

Site Status

Meeker County Memorial Hospital

Lichfield, Minnesota, United States

Site Status

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, United States

Site Status

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, United States

Site Status

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

CentraCare Clinic - River Campus

Saint Cloud, Minnesota, United States

Site Status

Coborn Cancer Center

Saint Cloud, Minnesota, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, United States

Site Status

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, United States

Site Status

HealthEast Cancer Care at St. Joseph's Hospital

Saint Paul, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, United States

Site Status

Ridgeview Medical Center

Waconia, Minnesota, United States

Site Status

HealthEast Cancer Care at Woodwinds Health Campus

Woodbury, Minnesota, United States

Site Status

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, United States

Site Status

Cancer Resource Center - Lincoln

Lincoln, Nebraska, United States

Site Status

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

Immanuel Medical Center

Omaha, Nebraska, United States

Site Status

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, United States

Site Status

Creighton University Medical Center

Omaha, Nebraska, United States

Site Status

Bismarck Cancer Center

Bismarck, North Dakota, United States

Site Status

Medcenter One Hospital Cancer Care Center

Bismarck, North Dakota, United States

Site Status

Mid Dakota Clinic, PC

Bismarck, North Dakota, United States

Site Status

St. Alexius Medical Center Cancer Center

Bismarck, North Dakota, United States

Site Status

CCOP - MeritCare Hospital

Fargo, North Dakota, United States

Site Status

MeritCare Broadway

Fargo, North Dakota, United States

Site Status

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, United States

Site Status

Wood County Oncology Center

Bowling Green, Ohio, United States

Site Status

Lima Memorial Hospital

Lima, Ohio, United States

Site Status

Northwest Ohio Oncology Center

Maumee, Ohio, United States

Site Status

St. Luke's Hospital

Maumee, Ohio, United States

Site Status

St. Charles Mercy Hospital

Oregon, Ohio, United States

Site Status

Toledo Clinic - Oregon

Oregon, Ohio, United States

Site Status

Firelands Regional Medical Center

Sandusky, Ohio, United States

Site Status

North Coast Cancer Care, Incorporated

Sandusky, Ohio, United States

Site Status

Flower Hospital Cancer Center

Sylvania, Ohio, United States

Site Status

Mercy Hospital of Tiffin

Tiffin, Ohio, United States

Site Status

Toledo Hospital

Toledo, Ohio, United States

Site Status

St. Vincent Mercy Medical Center

Toledo, Ohio, United States

Site Status

Medical University of Ohio Cancer Center

Toledo, Ohio, United States

Site Status

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

Site Status

Toledo Clinic, Incorporated - Main Clinic

Toledo, Ohio, United States

Site Status

Fulton County Health Center

Wauseon, Ohio, United States

Site Status

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, United States

Site Status

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States

Site Status

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, United States

Site Status

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Medical X-Ray Center, PC

Sioux Falls, South Dakota, United States

Site Status

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States

Site Status

Fredericksburg Oncology, Incorporated

Fredericksburg, Virginia, United States

Site Status

Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Green Bay Oncology, Limited at St. Mary's Hospital

Green Bay, Wisconsin, United States

Site Status

St. Mary's Hospital Medical Center - Green Bay

Green Bay, Wisconsin, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Franciscan Skemp Healthcare - La Crosse Campus

La Crosse, Wisconsin, United States

Site Status

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, United States

Site Status

Green Bay Oncology, Limited - Oconto Falls

Oconto Falls, Wisconsin, United States

Site Status

Green Bay Oncology, Limited - Sturgeon Bay

Sturgeon Bay, Wisconsin, United States

Site Status

Countries

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United States

References

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Tan WW, Allred JB, Salim M, Flynn P, Fishkin PA, Stella PJ, Wiesenfeld M, Bernath AM, Fitch TR, Perez EA. Phase II interventional study (N0337) of capecitabine in combination with vinorelbine and trastuzumab for first- or second-line treatment of HER2-positive metastatic breast cancer: a north central cancer treatment group trial. Clin Breast Cancer. 2012 Apr;12(2):81-6. doi: 10.1016/j.clbc.2012.01.001.

Reference Type RESULT
PMID: 22444716 (View on PubMed)

Chumsri S, Sperinde J, Liu H, Gligorov J, Spano JP, Antoine M, Moreno Aspitia A, Tan W, Winslow J, Petropoulos CJ, Chenna A, Bates M, Weidler JM, Huang W, Dueck A, Perez EA. High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance). Clin Cancer Res. 2018 Jul 1;24(13):3053-3058. doi: 10.1158/1078-0432.CCR-17-1864. Epub 2018 Mar 12.

Reference Type DERIVED
PMID: 29530935 (View on PubMed)

Other Identifiers

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NCI-2012-02625

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000390344

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCCTG-N0337

Identifier Type: -

Identifier Source: org_study_id

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