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Trastuzumab With or Without Paclitaxel in Treating Women With Metastatic Breast Cancer That Overexpresses HER2
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
First Received: March 7, 2000   Last Updated: February 6, 2009   History of Changes
Sponsored by: Swiss Group for Clinical Cancer Research
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004935
  Purpose

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether combining monoclonal antibody therapy with chemotherapy is more effective than antibody therapy alone in treating patients with metastatic breast cancer.

PURPOSE: This randomized phase III trial is studying trastuzumab and paclitaxel to see how well they work compared to trastuzumab alone in treating women with metastatic breast cancer that overexpresses HER2.


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

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Paclitaxel Trastuzumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: Randomized Phase III Trial of Herceptin Followed by Taxol Plus Herceptin Versus the Combination of Herceptin and Taxol as First-Line Chemotherapy in Patients With HER2-Overexpressing Advanced Breast Cancer

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

Primary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Time to first progression [ Designated as safety issue: No ]
  • Time to treatment failure as measured at completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: August 1999
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the efficacy and toxicity of first-line trastuzumab (Herceptin) alone followed at disease progression by combination trastuzumab and paclitaxel vs first-line combination trastuzumab and paclitaxel in women with HER2-overexpressing metastatic breast cancer.
  • Compare the quality of life of patients treated with these regimens.
  • Investigate the predictive value of serum HER2/neu ECD levels on clinical outcome, the effects of trastuzumab on estrogen receptor, and the association of immunoprofiles of erbB-1, erbB-2, erbB-3, and erbB-4 with clinical outcome in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to degree of HER2/neu-overexpression (2+ vs 3+), prior anthracycline-containing adjuvant treatment (no prior treatment vs prior treatment without radiotherapy to left chest wall vs prior treatment with radiotherapy to left chest wall), estrogen-receptor status (positive vs negative vs unknown), prior therapy (first-line vs second/third-line), and center. Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes weekly. At time of disease progression, patients receive combination trastuzumab IV and paclitaxel IV as in arm II.
  • Arm II: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes weekly. Paclitaxel is administered IV over 1 hour weekly for 3 weeks followed by 1 week of rest. Treatment continues in both arms in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and day 1 of courses 2, 3, 4, 5, 6, 8, 10 , and 12.

Patients are followed at 1, 3, and 6 months and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 170-250 patients (85-125 per arm) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed HER2-overexpressing metastatic breast carcinoma
  • Clinically or radiologically measurable or evaluable disease

    • Bidimensionally or unidimensionally measurable lesions
  • No ascitic, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as only indicator lesion
  • No known clinical brain or meningeal involvement
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 to 70

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-1 OR
  • SAKK 0-1

Life expectancy:

  • At least 12 weeks

Hematopoietic:

  • Hemoglobin at least 10 g/dL
  • Platelet count at least 100,000/mm^3
  • Absolute neutrophil count at least 2,000/mm^3

Hepatic:

  • Bilirubin normal
  • SGOT and/or SGPT no greater than 2 times upper limit of normal (ULN) (3 times ULN if proven liver metastases) OR
  • No SGOT and/or SGPT greater than 1.5 times ULN if alkaline phosphatase greater than 2.5 times ULN

Renal:

  • Creatinine no greater than 1.25 times ULN

Cardiovascular:

  • LVEF normal
  • No history of atrial ventricular arrhythmia, congestive heart failure, or angina pectoris, even if medically controlled
  • No history of second or third-degree heart blocks
  • No uncontrolled hypertension

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No pre-existing motor or sensory neuropathy grade 2 or greater
  • No psychiatric disorder that would preclude informed consent
  • No other prior malignancy except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No definite contraindications for use of corticosteroids
  • No other concurrent serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Prior adjuvant or neoadjuvant chemotherapy allowed
  • No more than 2 prior chemotherapy regimens for metastatic disease
  • No prior cumulative dose of doxorubicin greater than 240 mg/m^2
  • No prior cumulative dose of epirubicin greater than 360 mg/m^2
  • No prior taxanes

Endocrine therapy:

  • Prior hormonal therapy as adjuvant treatment or for metastatic disease allowed
  • No concurrent corticosteroids unless started more than 6 months prior to study and at low doses (i.e., no greater than 20 mg methylprednisolone or equivalent)

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • No other concurrent anticancer drugs
  • No other concurrent experimental drugs
  • No concurrent bisphosphonates unless initiated more than 3 months prior to study

    • Chronic use allowed provided bone metastases are not sole indicator lesions
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004935

Locations
Italy
European Institute of Oncology Recruiting
Milan, Italy, 20141
Contact: Aron Goldhirsch, MD     39-02-574-894-39     aron.goldhirsch@ibcsg.org    
Switzerland
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland, CH-1011
Contact: Lucien Perey, MD     41-21-314-0155     lucien.perey@chuv.hospvd.ch    
Inselspital Bern Recruiting
Bern, Switzerland, CH-3010
Contact: Stefan Aebi, MD     41-31-632-4114     stefan.aebi@insel.ch    
Kantonspital Aarau Recruiting
Aarau, Switzerland, CH-5001
Contact: Astrid Schonenberger, MD     41-62-838-6064        
Kantonsspital - St. Gallen Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Dagmar Hess, MD     41-71-494-1111     dagmar.hess@kssg.ch    
Universitaetsspital-Basel Recruiting
Basel, Switzerland, CH-4031
Contact: Christoph Rochlitz, MD     41-61-265-5059     crochlitz@uhbs.ch    
Ospedale Beata Vergine Recruiting
Mendrisio, Switzerland, CH-6850
Contact: Olivia Pagani, MD     41-91-811-3395        
Regionalspital Recruiting
Thun, Switzerland, 3600
Contact: Daniel Rauch     41-33-226-2626        
UniversitaetsSpital Zuerich Recruiting
Zurich, Switzerland, CH-8091
Contact: Bernhard Pestalozzi, MD     41-31-255-2214        
Kantonsspital Graubuenden Recruiting
Chur, Switzerland, CH-7000
Contact: Roger von Moos, MD     41-81-256-6111     roger.vonmoos@ksgr.ch    
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Aron Goldhirsch, MD European Institute of Oncology
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067621, SWS-SAKK-22/99, EU-99028
Study First Received: March 7, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00004935     History of Changes
Health Authority: Unspecified

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

Study placed in the following topic categories:
Skin Diseases
Paclitaxel
Tubulin Modulators
Trastuzumab
Breast Neoplasms
Antimitotic Agents
Antineoplastic Agents, Phytogenic
Breast Diseases
Recurrence

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 May 07, 2009