Trastuzumab With or Without Paclitaxel in Treating Women With Metastatic Breast Cancer That Overexpresses HER2

This study is currently recruiting patients.

Sponsored by

Swiss Institute for Applied Cancer Research

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: Randomized phase III trial to compare the effectiveness of the monoclonal antibody trastuzumab with or without paclitaxel in treating women who have metastatic breast cancer that overexpresses HER2.

Study Type: Treatment

Official Title: Phase III Randomized Study of Trastuzumab (Herceptin) Alone Followed By Paclitaxel Plus Trastuzumab Versus Upfront Combination of Trastuzumab and Paclitaxel in Women With HER2 Overexpressing Metastatic Breast Cancer

Further Study Details: OBJECTIVES: I. Compare efficacy and toxicity of the sequential administration of trastuzumab (Herceptin) alone followed at disease progression by the combination of trastuzumab and paclitaxel versus the upfront combination of both drugs in women with HER2 overexpressing metastatic breast cancer. II. Compare quality of life of these patients on these 2 regimens. III. 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.  PROTOCOL 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), 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 IV is administered over 1 hour weekly for 3 weeks followed by 1 week of rest. Treatment continues in both arms until unacceptable toxicity or disease progression. 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 340 patients (170 per arm) will be accrued for this study.  

Eligibility

Ages Eligible for Study:  18 Years    -   70 Years Criteria

PROTOCOL ENTRY 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 --Prior/Concurrent Therapy-- Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for advanced breast cancer No more than 1 prior neoadjuvant or adjuvant chemotherapy regimen At least 6 months since prior neoadjuvant or adjuvant chemotherapy No cumulative dose of doxorubicin greater than 240 mg/m2 No cumulative dose of epirubicin greater than 360 mg/m2 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 --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/mm3 Absolute neutrophil count at least 2,000/mm3 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 Neurologic: No preexisting motor or sensory neuropathy grade 2 or greater No psychiatric disorder that would preclude informed consent Other: Not pregnant or nursing Fertile patients must use effective contraception No history of a second neoplasm except for 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

Location and Contact Information

Italy

Istituto Europeo Di Oncologia, Milano,    20141,   Italy; Recruiting

Aron Goldhirsch       39-02-574-894-39   

Switzerland

Inselspital, Bern, Bern,    CH-3010,   Switzerland; Recruiting

Claude Gimmi       41-31-632-87-77   

Switzerland

Ospedale Beata Vergine, Mendrisio,    CH-6850,   Switzerland; Recruiting

Olivia Pagani       41-91-646-01-01   

Switzerland

Swiss Institute for Applied Cancer Research, Bern,   CH-3008,   Switzerland; Recruiting

Monica Castiglione-Gertsch       41-31-389-91-91   

Study chairs or principal investigators

Aron Goldhirsch,  Study Chair

Swiss Institute for Applied Cancer Research    

More Information

Study ID Numbers  199/14801;   SWS-SAKK-22/99; EU-99028

NLM Identifier  NCT00004935

Date study started August 30, 1999

Last Updated  March 1, 2000

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