Vorinostat and Trastuzumab in Treating Patients With Metastatic or Locally Recurrent Breast Cancer
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Vorinostat and trastuzumab also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving vorinostat together with trastuzumab may be a better way to block tumor growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat when given together with trastuzumab and to see how well they work in treating patients with metastatic breast canceror breast cancer that has recurred in the chest wall.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Trastuzumab (Herceptin) in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Her-2 Amplified Breast Cancer|
- Response Rate [ Time Frame: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy ] [ Designated as safety issue: No ]Tumor response is assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Response included complete response (CR) and partial response (PR). CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.
- Time to Progression [ Time Frame: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy ] [ Designated as safety issue: No ]Tumor response is assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Disease progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s). Time to progression is defined as time from registration to disease progression.
- Overall Survival [ Time Frame: Survival was assessed every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry ] [ Designated as safety issue: No ]Overall survival is defined as time from registration to death from any cause. Patients who were alive were censored as the last date of known alive.
|Study Start Date:||August 2006|
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
|Experimental: vorinostat +trastuzumab||
6 mg/kg once on Day 1, infused over 90 minutes, every 3 weeks
Other Names:Drug: vorinostat
200 mg of Suberoylanilide Hydroxamic Acid (SAHA) orally twice a day, daily for 14 days out of a 21-day cycle
- Determine the maximum tolerated dose (MTD) of vorinostat in combination with trastuzumab (Herceptin^®) in patients with metastatic or local chest wall recurrent HER-2-amplified breast cancer. (Phase I)
- Determine the toxic effects of this regimen in these patients. (Phase I)
- Determine the response rate in patients treated with this regimen. (Phase II)
- Determine the time to progression in patients treated with this regimen. (Phase II)
OUTLINE: This is an open-label, multicenter, dose-escalation study of vorinostat.
- Phase I: Patients receive oral vorinostat twice daily on days 1-14 and trastuzumab (Herceptin^®) intravenously (IV) over 90 minutes 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 vorinostat 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. At least 6 patients are treated at the MTD.
- Phase II: Patients receive vorinostat at the MTD and trastuzumab as in phase I. After completion of study treatment, patients are followed periodically for 3 years.
ACTUAL ACCRUAL: a total of 16 patients enrolled on the study.