A Phase III Study of Paclitaxel Via Weekly 1 Hour Infusion Versus Standard 3 Hour Infusion Every 3 Weeks With Herceptin (Trastuzumab) (NSC #688097) in the Treatment of Patients With/Without HER-2/Neu-Overexpressing Metastatic Breast Cancer
I. To determine whether "dose dense" (DD) treatment with paclitaxel via weekly 1-hour
infusion has a significantly higher response rate than "standard" (S) paclitaxel treatment,
regardless of human epidermal growth factor receptor 2 (HER-2/neu) status and assignment to
II. To determine if the addition of Herceptin to DD or S paclitaxel significantly improves
the response rate as compared to DD or S paclitaxel alone for HER-2/neu non-overexpressing
metastatic breast cancer (e.g., 0 or 1+).
III. To determine whether the addition of Herceptin to chemotherapy treatment modifies the
quality of life experienced by patients with HER-2/neu non-overexpressing metastatic breast
IV. To determine whether the quality of life experienced by patients with metastatic breast
cancer who have been treated with "standard" paclitaxel treatment differ from that of
patients treated with "dose dense" paclitaxel treatment.
V. To correlate amplification and overexpression of the growth factor receptor ErbB2 by
immunohistochemistry and fluorescent in-situ hybridization (FISH) with response rate, time
to progression, and overall survival of patients with metastatic breast cancer treated with
paclitaxel chemotherapy and paclitaxel + Herceptin.
VI. To correlate ErbB2 shed extracellular domain (ECD) with response rate, time to
progression, and overall survival of patients with metastatic breast cancer treated with
different doses and schedules of paclitaxel and paclitaxel + Herceptin. In addition, to
follow patterns of ErbB2/ECD after treatment and upon relapse.
I. To evaluate time to progression and survival of patients with HER-2 overexpressing
metastatic breast cancer treated with either DD or S paclitaxel plus weekly Herceptin.
II. To evaluate time to progression and survival of patients with HER-2 non-overexpressing
metastatic breast cancer treated with either DD or S paclitaxel alone or DD or S paclitaxel
plus weekly Herceptin.
III. To evaluate cardiac toxicity as measured by changes in LVEF from baseline to follow-up
OUTLINE; Patients are assigned to 1 of 2 treatment groups.
GROUP I (HER2/neu non-overexpressors): Patients are randomized to 1 of 4 treatment arms.
ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.
ARM B: Patients receive paclitaxel IV over 1 hour weekly.
ARM C: Patients receive paclitaxel as in Arm A. Patients also receive trastuzumab IV weekly.
ARM D: Patients receive paclitaxel as in Arm B and trastuzumab as in Arm C.
GROUP II (HER2/neu overexpression): Patients are assigned to 1 of 2 treatment arms.
ARM E: Patients receive paclitaxel and trastuzumab as in Arm C.
ARM F: Patients receive paclitaxel and trastuzumab as in Arm D.
In all arms, courses repeat every 3 weeks in the absence of disease progression or
After the completion of study treatment, patients are followed up periodically for up to 5
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Response rate (complete response [CR]) and partial response [PR])
Multivariate logistic regression will be used to relate patient characteristics and pretreatment clinical variables with tumor response (complete or partial). Interim analyses will use a chi square statistic to compare response incidence by treatment arm with two-sided bounds constructed from the O'Brien-Fleming approach
Up to 5 years
Cancer and Leukemia Group B
United States: Food and Drug Administration
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