Chemotherapy Plus Trastuzumab in Treating Patients With Breast Cancer
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 I trial to study the effectiveness of vinorelbine plus trastuzumab in treating patients who have refractory or metastatic breast cancer.
Drug: vinorelbine ditartrate
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Clinical Trial Of Vinorelbine (Navelbine) And Trastuzumab (Herceptin) In Patients With Carcinoma Of The Breast Or Non-Small Cell Lung Cancer And HER-2/NEU Overexpression|
|Study Start Date:||November 1999|
|Primary Completion Date:||September 2002 (Final data collection date for primary outcome measure)|
Trastuzumab (INN; trade name Herceptin) is a monoclonal antibody that interferes with the HER2/neu receptor. Its main use is to treat certain breast cancers.
The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off. The HER proteins regulate cell growth, survival, adhesion, migration, and differentiation—functions that are amplified or weakened in cancer cells. In some cancers, notably some breast cancers, HER2 is over-expressed, and causes breast cells to reproduce uncontrollably.
- Determine the maximum tolerated dose of vinorelbine in combination with trastuzumab (Herceptin) in patients with HER-2/neu overexpressing unresectable or metastatic non-small cell lung cancer (closed to accrual as of 4/16/01) or refractory locally advanced or metastatic breast cancer.
- Determine the pharmacokinetic and pharmacodynamic profiles of this regimen in this patient population.
- Determine the objective response rate of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of vinorelbine.
Patients receive vinorelbine IV over 5-10 minutes on days 1 and 8, and trastuzumab (Herceptin) IV over 30-90 minutes on days 8 and 15 of course 1 and days 1, 8, and 15 of all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3 to 6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 30-35 patients will be accrued for this study.
|United States, New Hampshire|
|Norris Cotton Cancer Center|
|Lebanon, New Hampshire, United States, 03756-0002|
|Study Chair:||Peter A. Kaufman, MD||Norris Cotton Cancer Center|