Lonafarnib, Trastuzumab, and Paclitaxel in Treating Patients With HER2/Neu-Overexpressing Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
Summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining lonafarnib and trastuzumab with paclitaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with trastuzumab and paclitaxel in treating patients with HER2/neu-overexpressing stage IIIB, stage IIIC, or stage IV breast cancer.
Description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of lonafarnib in combination with trastuzumab (Herceptin®) and paclitaxel in patients with HER2/neu-overexpressing stage IIIB, IIIC, or IV breast cancer.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
Secondary
- Determine the pharmacokinetic profiles of these drugs in these patients.
- Correlate the pharmacodynamics with the pharmacokinetics of this regimen in these patients.
- Correlate the pharmacokinetics and pharmacodynamics of this regimen with observed toxicity in these patients.
- Determine the response to this regimen in patients with measurable disease.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of lonafarnib.
- Course 1: Patients receive a loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 and over 30 minutes on days 8 and 15. Patients also receive paclitaxel IV over 3 hours on day 1.
- Course 2: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 2. Patients also receive oral lonafarnib twice daily on days 3-21.
- Course 3 and all subsequent courses: Patients receive oral lonafarnib twice daily on days 1-21; trastuzumab IV over 30 minutes on days 1, 8, and 15; and paclitaxel IV over 3 hours on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of lonafarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed every 8 weeks until disease progression.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.
Study Design
Masking: Open Label, Primary Purpose: Treatment
Conditions
Breast Cancer
Intervention
trastuzumab, lonafarnib, paclitaxel
Location
Institut Jules Bordet
Brussels
Belgium
1000
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00068757
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:54:57-0400
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Medical and Biotech [MESH] Definitions
Trastuzumab
A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.
Breast Cancer Lymphedema
Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
Carcinoma, Lobular
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
Capecitabine
A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.
