Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

Breast Cancer Clinical Trial

Official title:

Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel (+/- Trastuzumab) Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00574587
• Other study ID #: 07-10-374
• Secondary ID: NYCC1NCI-2013-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2007
• Est. completion date: May 2014

Study information

• Verified date: September 2020
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Vorinostat
Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
• Paclitaxel
Paclitaxel 80 mg/m2 weekly for 12 weeks
• Trastuzumab
Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
• Doxorubicin
Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
• Cyclophosphamide
Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks

Procedure:
• Surgery
Surgical excision of tumor from breast

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York

Sponsors (2)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab	Dose limiting toxicity in cycle 1	3 weeks
Secondary	Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer.	Pathological Complete Response (CR) defined as absence of invasive cancer at surgery	6 months