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Combination Chemotherapy With or Without Trastuzumab in Treating Women With Metastatic Breast Cancer
This study has been completed.
First Received: March 7, 2000   Last Updated: May 29, 2009   History of Changes
Sponsor: Eastern Cooperative Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004888
  Purpose

RATIONALE: Drugs used in chemotherapy 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.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with or without trastuzumab in treating women who have metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: docetaxel
Drug: pegylated liposomal doxorubicin hydrochloride
Phase II

Study Type: Interventional
Study Design: Treatment
Official Title: A Safety and Efficacy Study of Doxil and Taxotere +/- Herceptin in Advanced Breast Cancer

Resource links provided by NLM:


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

Study Start Date: October 2000
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Assess the safety, toxicity, and feasibility of doxorubicin HCl liposome and docetaxel with or without trastuzumab (Herceptin™) in patients with metastatic breast cancer, particularly with respect to cardiotoxicity.
  • Assess the overall objective response rate, response duration, time to treatment failure, and median survival of these patients with these treatment regimens.
  • Assess any association between trough plasma levels of cardiac troponin T and brain natriuretic peptide and any cardiac event (congestive heart failure or LVEF decrease).

OUTLINE: Patients are assigned to one of two treatment arms according to HER2 overexpression status.

  • Arm I (HER2 nonoverexpressed): Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

  • Arm II (HER2 overexpressed): Patients receive trastuzumab IV over 90 minutes on day 1, with subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3 weeks for 8 courses.

Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 92 patients (46 per arm) will be accrued for this study within 13 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic adenocarcinoma of the breast
  • HER2 nonoverexpressed (0-1+) OR overexpressed (2-3+)
  • Measurable or evaluable disease

    • Pleural or peritoneal effusions allowed if local intracavitary treatment not started at onset of therapy
    • Blastic or mixed blastic/lytic osseous metastases allowed if accompanied by pain or decreased performance status, and do not require radiotherapy within two courses of study therapy
    • Osteolytic disease allowed if proven by x-ray
    • No abnormal bone scan without confirmatory x-rays as only evidence of metastatic disease
  • Prior brain metastases responsive to treatment of radiotherapy and/or surgery allowed (cannot be only site of metastases)
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

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

Hepatic:

  • SGOT no greater than 2.5 times upper limit of normal
  • Bilirubin normal

Renal:

  • Creatinine no greater than 1.5 mg/dL

Cardiovascular:

  • No prior deep venous thrombosis or thromboembolic condition
  • LVEF at least lower limit of normal
  • No prior myocardial infarction or congestive heart failure
  • No arrhythmia requiring medication
  • No hypertension or systolic or diastolic dysfunction
  • No ventricular hypertrophy or conduction abnormality

Pulmonary:

  • No prior pulmonary thromboembolism

Other:

  • No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
  • Not pregnant or nursing
  • Fertile women must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior trastuzumab (Herceptin™)

Chemotherapy:

  • No prior chemotherapy for advanced or local/regional recurrent disease
  • Prior adjuvant chemotherapy allowed if completed 6 months before metastasis
  • No prior anthracyclines or anthracenediones

Endocrine therapy:

  • At least 2 weeks since prior hormonal therapy

Radiotherapy:

  • Prior radiotherapy allowed only to conserved breast, postmastectomy chest wall with or without internal mammary lymph node chain (IMN), or field containing less than 25% bone marrow
  • No prior photon IMN treatment
  • At least 2 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery:

  • At least 2 weeks since surgery (including mastectomy) and recovered
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004888

  Hide Study Locations
Locations
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, New Jersey
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
United States, New York
Albert Einstein Clinical Cancer Center
Bronx, New York, United States, 10461
MBCCOP-Our Lady of Mercy Cancer Center
Bronx, New York, United States, 10466
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
CCOP - Columbus
Columbus, Ohio, United States, 43206
MetroHealth's Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
CCOP - MainLine Health
Wynnewood, Pennsylvania, United States, 19096
Lankenau Cancer Center at Lankenau Hospital
Wynnewood, Pennsylvania, United States, 19096
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54307-3453
South Africa
Pretoria Academic Hospital
Pretoria, South Africa, 0001
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Antonio C. Wolff, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Wolff AC, Wang M, Sparano JA, et al.: Cardiac safety and clinical activity of pegylated liposomal doxorubicin (D) and docetaxel (T) with and without trastuzumab (H) as 1st line chemotherapy in HER2-positive and HER2-negative metastatic breast cancer (MBC): Eastern Cooperative Oncology Group (ECOG) trial E3198. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-3040, 2004.
Wolff AC, Bonetti M, Sparano JA, et al.: Cardiac safety of trastuzumab (H) in combination with pegylated liposomal doxorubicin (D) and docetaxel (T) in HER2-positive metastatic breast cancer (MBC): preliminary results of the Eastern Cooperative Oncology Group trial E3198. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-70, 2003.

Study ID Numbers: CDR0000067564, ECOG-3198
Study First Received: March 7, 2000
Last Updated: May 29, 2009
ClinicalTrials.gov Identifier: NCT00004888     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Docetaxel
Neoplasms
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Therapeutic Uses
Trastuzumab
Breast Neoplasms
Antibiotics, Antineoplastic
Pharmacologic Actions
Doxorubicin
Breast Diseases

ClinicalTrials.gov processed this record on November 27, 2009