S0215 Trastuzumab, Docetaxel, Vinorelbine, and Filgrastim in Treating Women With Stage IV Breast Cancer

Docetaxel (NSC-628503) And Vinorelbine (NSC-608210) Plus Filgrastim (NSC-614629) With Weekly Trastuzumab (NSC-688097) For HER-2 Positive, Stage IV Breast Cancer

RATIONALE: Drugs used in chemotherapy 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. Colony-stimulating factors, such as filgrastim, may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with docetaxel, vinorelbine, and filgrastim in treating women who have stage IV breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Biological: filgrastim; Biological: trastuzumab; Drug: vinorelbine

Detailed Description

OBJECTIVES:

• Determine the 1-year survival of women with HER2-positive stage IV breast cancer treated with trastuzumab (Herceptin), docetaxel, and vinorelbine with filgrastim (G-CSF) support.
• Determine the response rate (complete and partial, confirmed and unconfirmed) in the subset of patients with measurable disease treated with this regimen.
• Determine the progression-free survival of patients treated with this regimen.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Obtain tissue blocks for the determination of predictors of response (e.g., beta-tubulin mutations) to microtubule interacting agents in this patient population and for other future studies.

OUTLINE: This is a pilot, multicenter study.

Patients receive docetaxel IV over 1 hour on day 1, filgrastim (G-CSF) subcutaneously on days 2-21, vinorelbine IV over 6-10 minutes on days 8 and 15, and trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. If docetaxel and vinorelbine are discontinued due to unacceptable toxicity, patients may continue to receive trastuzumab. If trastuzumab is discontinued due to unacceptable toxicity, patients may continue to receive chemotherapy with G-CSF support.

Patients are followed every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18-22.5 months.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arkansas
    • Ft. Smith, Arkansas, United States, 72903
      • Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
    • Jonesboro, Arkansas, United States, 72401-9320
      • Ben E. Owens Cancer Treatment Center at St. Bernard's Medical Center
  • California
    • Castro Valley, California, United States, 94546
      • Eden Medical Center
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94602
      • Highland General Hospital at St. George's University School of Medicine
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center - San Pablo Campus
  • Florida
    • Pensacola, Florida, United States, 32514
      • West Florida Cancer Institute at West Florida Hospital - Pensacola
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Mountain States Tumor Institute - Boise
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Mt. Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital Cancer Center
    • Naperville, Illinois, United States, 60540
      • Hematology Oncology Consultants - Naperville
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Salina, Kansas, United States, 67401
      • Tammy Walker Cancer Center at Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, PA - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Bay City, Michigan, United States, 48708
      • Bay Regional Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Mount Clemens, Michigan, United States, 48043
      • Ted B. Wahby Cancer Center at Mount Clemens General Hospital
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Saint Francis Medical Center
    • Gape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
    • St. Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare
    • Billings, Montana, United States, 59107-5100
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59107-7000
      • Deaconess Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • St. James Community Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital - Ridgewood
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Research and Treatment Center
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates, PC
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Medical Center
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Regional Cancer Center at Forsyth Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Independence, Ohio, United States, 44131
      • Community Oncology Group at Cleveland Clinic Cancer Center
    • Mansfield, Ohio, United States, 44903
      • MedCentral - Mansfield Hospital
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97213-2967
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center & Children's Hospital
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • Texas
    • Galveston, Texas, United States, 77555-0361
      • University of Texas Medical Branch
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
    • San Antonio, Texas, United States, 78209
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • University Hospital - San Antonio
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
    • Salt Lake City, Utah, United States, 84103
      • Latter Day Saints Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
  • Washington
    • Auburn, Washington, United States, 98002
      • Auburn Regional Center for Cancer Care
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Centralia, Washington, United States, 98531-9027
      • Providence Centralia Hospital Regional Cancer Center
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Mt. Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Olympia, Washington, United States, 98507
      • Capital Medical Center
    • Olympia, Washington, United States, 98506-5166
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
    • Sedro-Wooley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
    • Tacoma, Washington, United States, 98405-3004
      • St. Joseph Medical Center at Franciscan Health System
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV breast cancer

  • Metastasis to the ipsilateral supraclavicular lymph nodes allowed
• HER2-positive by fluorescence in situ hybridization (FISH) or immunohistochemistry 3+ staining confirmed in the adjuvant or metastatic setting
• No effusions or ascites as only sites of disease
• No primary or metastatic brain or central nervous system tumor

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• aspartate aminotransferase or Alanine aminotranferease no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Not specified

Cardiovascular:

• left ventricular ejection fraction normal by multigated radionuclide angiography or echocardiogram (patients who have received prior anthracycline therapy)
• No clinical evidence or history of cardiomyopathy

Other:

• No pre-existing grade 2 or greater motor or sensory peripheral neuropathy except abnormalities due to cancer
• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with Polysorbate 80
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other adequately treated stage I or II cancer currently in complete remission
• No known sensitivity to E. coli-derived proteins
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 6 months since prior chemotherapy
• Prior anthracycline as adjuvant therapy allowed
• No prior cumulative dose of doxorubicin more than 360 mg/m^2
• No prior cumulative dose of epirubicin more than 720 mg/m^2
• No more than 1 prior adjuvant or neoadjuvant chemotherapy regimen for primary disease
• No prior docetaxel
• No prior vinorelbine
• Prior paclitaxel allowed

Endocrine therapy:

• Prior hormonal therapy as adjuvant therapy or for metastatic breast cancer allowed
• No concurrent hormonal therapy

Radiotherapy:

• At least 3 weeks since prior radiotherapy

Surgery:

• At least 2 weeks since prior surgery and recovered

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab, docetaxel, vinorelbine and filgrastim	Drug: docetaxel; Biological: filgrastim; Biological: trastuzumab; Drug: vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival at 1 Year	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival		2 years
Response Rate (Complete and Partial, Confirmed and Unconfirmed)	Response was measured by the RECIST criteria. A patient was considered a responder if there was confirmed or unconfirmed partial or complete response. All others were considered non-responders even if the patient was technically not assessable due to different measurement techniques at the two time points.	response assessed after every 3 cycles (9 weeks) during treatment for up to 3 years if no progession
Toxicity	Number of patients for whom highest grade of toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported.	toxicities assessed every 3 weeks during treatment, for up to 3 years if no progession

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Joseph J. Kash, MD, Edward Hospital Cancer Center

Publications and helpful links

General Publications

• Livingston RB, Barlow WE, Kash JJ, Albain KS, Gralow JR, Lew DL, Flaherty LE, Royce ME, Hortobagyi GN. SWOG S0215: a phase II study of docetaxel and vinorelbine plus filgrastim with weekly trastuzumab for HER2-positive, stage IV breast cancer. Breast Cancer Res Treat. 2011 Nov;130(1):123-31. doi: 10.1007/s10549-011-1698-5. Epub 2011 Aug 9.

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: July 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 6, 2013
• Last Update Submitted That Met QC Criteria: May 20, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab; Vinorelbine
• Other Study ID Numbers: CDR0000069440; U10CA032102 (U.S. NIH Grant/Contract); S0215 (Other Identifier: SWOG)