Trial for Locally Advanced Her2 Positive Breast Cancer Using Paclitaxel, Trastuzumab, Doxorubicin and Cyclophasmide on a Weekly Basis

This study is ongoing, but not recruiting participants.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Albert Einstein College of Medicine of Yeshiva University Identifier:
First received: December 13, 2007
Last updated: July 13, 2015
Last verified: July 2015
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.

Condition Intervention Phase
Breast Cancer
Drug: Vorinostat
Drug: Paclitaxel
Drug: Trastuzumab
Drug: Doxorubicin
Drug: Cyclophosphamide
Procedure: Mastectomy or Lumpectomy
Drug: Post surgery therapy (Trastuzumab)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel and Trastuzumab Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer

Resource links provided by NLM:

Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • To determine the recommended phase II dose of vorinostat in combination with weekly paclitaxel/trastuzumab [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the pathological CR rate in patients with Her2/neu positive locally advanced breast cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 54
Study Start Date: December 2007
Estimated Study Completion Date: January 2016
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Vorinostat
Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Drug: Paclitaxel
Paclitaxel 80 mg/m2 weekly for 12 weeks
Drug: Trastuzumab
Part A: Trastuzumab 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Drug: Doxorubicin
Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Procedure: Mastectomy or Lumpectomy
Surgical excision of tumor from breast
Drug: 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


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00574587

United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Merck Sharp & Dohme Corp.
Principal Investigator: Joseph Sparano, MD Montefiore Medical Center
  More Information

Responsible Party: Albert Einstein College of Medicine of Yeshiva University Identifier: NCT00574587     History of Changes
Other Study ID Numbers: 07-10-374  NYCC1  NCI-2013-01216 
Study First Received: December 13, 2007
Last Updated: July 13, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Albert Einstein College of Medicine of Yeshiva University:
Neoadjuvant Chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Liposomal doxorubicin
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors processed this record on May 04, 2016