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

Breast Cancer Clinical Trial

Official title:

Phase II Study of Capecitabine in Combination With Vinorelbine and Trastuzumab for the First- or Second-LineTreatment of HER2+ Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00093808
• Other study ID #: NCCTG-N0337
• Secondary ID: NCI-2012-02625CD
• Status: Completed
• Phase: Phase 2
• First received: October 6, 2004
• Last updated: August 12, 2016
• Start date: August 2004
• Est. completion date: May 2013

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: May 2013
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• capecitabine

• vinorelbine tartrate

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Howard Community Hospital	Kokomo	Indiana
United States	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Meeker County Memorial Hospital	Lichfield	Minnesota
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	McDonough District Hospital	Macomb	Illinois
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Firelands Regional Medical Center	Sandusky	Ohio
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-pos — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate as measured by RECIST criteria		Up to 5 years	No
Secondary	Time to progression as measured by RECIST criteria		Up to 5 years	No
Secondary	Duration of response as measured by RECIST criteria		Up to 5 years	No
Secondary	Overall survival as assessed by time		Up to 5 years	No
Secondary	Safety as assessed by CTC3		Up to 5 years	Yes