Brief Summary
Vorinostat is a histone deacetylase (HDAC) inhibitor which is approved by the U.S. Food and Drug Administration for the treatment of a rare type of cancer involving the skin (cutaneous T cell lymphoma), but not for breast cancer. HDAC inhibitors work by unsilencing tumor suppressor genes and other genes in the cancer cells that are repressed; when the genes are turned back on by the drug, it leads to death of the cancer cells. HDAC inhibitors such as vorinostat have been shown to enhance the effects of chemotherapy and trastuzumab in experimental systems. The purpose of this trial is to determine the optimal dose of vorinostat to use in combination with standard chemotherapy alone (or in combination with plus trastuzumab for HER2-positive disease), and to determine whether vorinostat enhances the effectiveness of standard chemotherapy (+/- trastuzumab) in patients with locally advanced breast cancer.
Brief Title
Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy
Detailed Description
This is a phase I-II trial in which patients with stage IIB-IIIC breast cancer will receive:
1. Neoadjuvant weekly paclitaxel (80 mg/m2 IV weekly x 12 weeks) plus vorinostat (200 or 300 mg PO BID on days 1-3 each paclitaxel dose) and trastuzumab (4 mg/kg loading dose, 2 mg/kg IV weekly x 12 total doses if HER2 positive, followed by:
2. Doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 2 weeks x 4 cycles (plus G-CSF), followed by:
3. Surgery (lumpectomy or mastectomy)
1. Neoadjuvant weekly paclitaxel (80 mg/m2 IV weekly x 12 weeks) plus vorinostat (200 or 300 mg PO BID on days 1-3 each paclitaxel dose) and trastuzumab (4 mg/kg loading dose, 2 mg/kg IV weekly x 12 total doses if HER2 positive, followed by:
2. Doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 2 weeks x 4 cycles (plus G-CSF), followed by:
3. Surgery (lumpectomy or mastectomy)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the breast associated with the following stages: IIB, IIIA, IIIB or IIIC.
* Tumor must be Her2/neu positive
* No prior chemotherapy, radiation or definitive therapeutic surgery
Exclusion Criteria:
* May not be receiving any other investigational agents
* Uncontrolled intercurrent illness
* Histologically or cytologically confirmed adenocarcinoma of the breast associated with the following stages: IIB, IIIA, IIIB or IIIC.
* Tumor must be Her2/neu positive
* No prior chemotherapy, radiation or definitive therapeutic surgery
Exclusion Criteria:
* May not be receiving any other investigational agents
* Uncontrolled intercurrent illness
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the breast associated with the following stages: IIB, IIIA, IIIB or IIIC.
* Tumor must be Her2/neu positive
* No prior chemotherapy, radiation or definitive therapeutic surgery
* Histologically or cytologically confirmed adenocarcinoma of the breast associated with the following stages: IIB, IIIA, IIIB or IIIC.
* Tumor must be Her2/neu positive
* No prior chemotherapy, radiation or definitive therapeutic surgery
Gender
Female
Gender Based
false
Keywords
Vorinostat
Neoadjuvant Chemotherapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT00574587
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
07-10-374
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel (+/- Trastuzumab) Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer
Primary Outcomes
Outcome Description
Dose limiting toxicity in cycle 1
Outcome Measure
Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab
Outcome Time Frame
3 weeks
Secondary Ids
Secondary Id
NYCC1
Secondary Id
NCI-2013-01216
Secondary Outcomes
Outcome Description
Pathological Complete Response (CR) defined as absence of invasive cancer at surgery
Outcome Time Frame
6 months
Outcome Measure
Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer.
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404