Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00368875
Status:
COMPLETED
Last Update Posted:
2015-11-05
First Post:
2006-08-24
Brief Title:
Phase I-II Study of Vorinostat Paclitaxel and Bevacizumab in Metastatic Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase III Study of a Combination of Suberoylanilide Hydroxamic Acid Vorinostat Plus Paclitaxel and Bevacizumab in Patients With Advanced Metastatic andor Local Chest Wall Recurrent Breast Cancer
Status:
COMPLETED
Status Verified Date:
2014-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial is studying the side effects and best dose of vorinostat when given together with paclitaxel and bevacizumab and to see how well they work in treating patients with metastatic breast cancer andor breast cancer that has recurred in the chest wall and cannot be removed by surgery Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Drugs used in chemotherapy such as paclitaxel work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Monoclonal antibodies such as bevacizumab 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 Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor Giving vorinostat together with paclitaxel and bevacizumab may kill more tumor cells
Detailed Description:
PRiMARY OBJECTIVES
I To determine the recommended phase II dose of oral suberoylanilide hydroxamic acid vorinostat in combination with weekly paclitaxel and bevacizumab in patients with chest wall recurrent or metastatic breast cancer Phase I II To determine the efficacy response rate response duration time to disease progression time to treatment failure and overall survival and toxicity of oral suberoylanilide hydroxamic acid vorinostat in combination with weekly paclitaxel and bevacizumab in patients with chest wall recurrent or metastatic breast cancer Phase II
SECONDARY OBJECTIVES
I To determine whether in vivo treatment with vorinostat induces a acetylation of proteins including histone H3 and H4 b ubiquitylation of proteins and c the levels of p21 and p27 levels in the peripheral blood mononuclear cells pre treatment vs cycle 1 day 2 after 3 VORINOSTAT doses but prior to paclitaxel
II To determine whether in vivo treatment with vorinostat induces a acetylation of proteins including histone H3 and H4 ubiquitylation of proteins and c the levels of Bim Bak tBID p21 and p27 levels as well as down regulate Bcl-2 Bcl-xL and survivin in chest wall recurrent or metastatic breast cancer cells pre treatment vs cycle 1 day 2 after 3 vorinostat doses but prior to paclitaxel
III To determine whether in the primary breast cancer and metastatic cancer if available pretreatment levels of Her-2 Estrogen Receptor ER-alpha Progesterone Receptor PR p21 p27 p-AKT p-ERK12 HDAC1 2 3 4 6 10 and SIRT2 levels predict for the response to treatment with VORINOSTAT plus paclitaxel
OUTLINE This is a phase I multicenter dose-escalation study of vorinostat SAHA followed by a phase II open-label study
Phase I Patients receive oral SAHA twice daily on days 1-3 8-10 and 15-17 paclitaxel IV over 1 hour on days 2 9 and 16 and bevacizumab IV over 30-90 minutes on days 2 and 16 Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of SAHA 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 The recommended phase II dose is defined as one dose level below the MTD
Phase II Patients receive SAHA at the recommended phase II dose and paclitaxel and bevacizumab as in phase I
I To determine the recommended phase II dose of oral suberoylanilide hydroxamic acid vorinostat in combination with weekly paclitaxel and bevacizumab in patients with chest wall recurrent or metastatic breast cancer Phase I II To determine the efficacy response rate response duration time to disease progression time to treatment failure and overall survival and toxicity of oral suberoylanilide hydroxamic acid vorinostat in combination with weekly paclitaxel and bevacizumab in patients with chest wall recurrent or metastatic breast cancer Phase II
SECONDARY OBJECTIVES
I To determine whether in vivo treatment with vorinostat induces a acetylation of proteins including histone H3 and H4 b ubiquitylation of proteins and c the levels of p21 and p27 levels in the peripheral blood mononuclear cells pre treatment vs cycle 1 day 2 after 3 VORINOSTAT doses but prior to paclitaxel
II To determine whether in vivo treatment with vorinostat induces a acetylation of proteins including histone H3 and H4 ubiquitylation of proteins and c the levels of Bim Bak tBID p21 and p27 levels as well as down regulate Bcl-2 Bcl-xL and survivin in chest wall recurrent or metastatic breast cancer cells pre treatment vs cycle 1 day 2 after 3 vorinostat doses but prior to paclitaxel
III To determine whether in the primary breast cancer and metastatic cancer if available pretreatment levels of Her-2 Estrogen Receptor ER-alpha Progesterone Receptor PR p21 p27 p-AKT p-ERK12 HDAC1 2 3 4 6 10 and SIRT2 levels predict for the response to treatment with VORINOSTAT plus paclitaxel
OUTLINE This is a phase I multicenter dose-escalation study of vorinostat SAHA followed by a phase II open-label study
Phase I Patients receive oral SAHA twice daily on days 1-3 8-10 and 15-17 paclitaxel IV over 1 hour on days 2 9 and 16 and bevacizumab IV over 30-90 minutes on days 2 and 16 Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of SAHA 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 The recommended phase II dose is defined as one dose level below the MTD
Phase II Patients receive SAHA at the recommended phase II dose and paclitaxel and bevacizumab as in phase I
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2012-03012 | REGISTRY | None | None |
| 06-05-291 | OTHER | None | None |
| 7703 | OTHER | None | None |
| N01CM62204 | NIH | None | None |
| N01CM62207 | NIH | None | None |
| N01CM62205 | NIH | None | None |
| N01CM62209 | NIH | CTEP | httpsreporternihgovquickSearchN01CM62209 |