This trial is active, not recruiting.

Condition breast cancer
Treatments vorinostat, paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, mastectomy or lumpectomy, post surgery therapy (trastuzumab)
Phase phase 1/phase 2
Targets HDAC, HER2
Sponsor Albert Einstein College of Medicine of Yeshiva University
Collaborator Merck Sharp & Dohme Corp.
Start date December 2007
End date May 2014
Trial size 54 participants
Trial identifier NCT00574587, 07-10-374, NCI-2013-01216, NYCC1


Chemotherapy plus trastuzumab (Herceptin) are standard treatments for breast cancer. There are circumstances where these treatments are given prior to surgery to reduce the size of the cancer and imptove the surgical outcome. In this trial, an oral drug called "vorinostat" will be given in combination with chemotherapy and trastuzumab. 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 plus trastuzumab, and to determine whether vorinostat enhances the effectiveness of standard chemotherapy plus trastuzumab.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Paclitaxel 80 mg/m2 weekly for 12 weeks
Part A: Trastuzumab 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
mastectomy or lumpectomy
Surgical excision of tumor from breast
post surgery therapy (trastuzumab)
Part D: After Surgical intervention Post Protocol Therapy- Trastuzumab 8 mg/kg as a loading dose, then 6 mg/kg every 3 weeks for a total of 14 doses

Primary Outcomes

To determine the recommended phase II dose of vorinostat in combination with weekly paclitaxel/trastuzumab
time frame: 1 year

Secondary Outcomes

To determine the pathological CR rate in patients with Her2/neu positive locally advanced breast cancer.
time frame: 2 years

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

Official title Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel and Trastuzumab Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer
Principal investigator Joseph Sparano, MD
Trial information was received from ClinicalTrials.gov and was last updated in July 2015.
Information provided to ClinicalTrials.gov by Albert Einstein College of Medicine of Yeshiva University.