Chemotherapy Plus Trastuzumab in Treating Patients With Breast Cancer

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
OBJECTIVES: 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.

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

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Biological: trastuzumab
* Drug: vinorelbine ditartrate


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed unresectable or metastatic non-small cell lung cancer Stage IIIB or IV (closed to accrual as of 4/16/01) OR Histologically confirmed locally advanced breast cancer that has progressed after first-line chemotherapy or metastatic breast cancer HER-2/neu overexpression (1+ to 3+) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) ALT no greater than 3 times ULN Renal: Creatinine no greater than 2 times ULN Cardiovascular: No prior or concurrent unstable angina No prior symptomatic congestive heart failure No myocardial infarction within the past 6 months LVEF at least 45% by echocardiogram or MUGA if received prior anthracycline or anthrapyrazole therapy Other: No prior hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of these products No other medical illness that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior trastuzumab (Herceptin) Chemotherapy: See Disease Characteristics No prior vinorelbine Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: trastuzumab|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.|
|Drug: vinorelbine ditartrate|Vinorelbine (trade name Navelbine) is an anti-mitotic chemotherapy drug that is given as a treatment for some types of cancer, including breast cancer and non-small cell lung cancer.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV breast cancer, stage IIIA breast cancer, recurrent breast cancer, stage IIIB breast cancer