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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	54 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	December 2007
Actual Primary Completion Date :	May 2014
Estimated Study Completion Date :	January 2016

Arms and Interventions

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Arm

Intervention/treatment

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

Outcome Measures

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Primary Outcome Measures :

1. To determine the recommended phase II dose of vorinostat in combination with weekly paclitaxel/trastuzumab [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. To determine the pathological CR rate in patients with Her2/neu positive locally advanced breast cancer. [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461

Sponsors and Collaborators

Albert Einstein College of Medicine, Inc.

Merck Sharp & Dohme Corp.

Investigators

Principal Investigator:	Joseph Sparano, MD	Montefiore Medical Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Albert Einstein College of Medicine, Inc.
ClinicalTrials.gov Identifier:	NCT00574587 History of Changes
Other Study ID Numbers:	07-10-374; NYCC1; NCI-2013-01216 ( Registry Identifier: CTRP )
First Posted:	December 17, 2007
Last Update Posted:	July 14, 2015
Last Verified:	July 2015

Keywords provided by Albert Einstein College of Medicine, Inc.:

Vorinostat; Neoadjuvant Chemotherapy

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Liposomal doxorubicin; Vorinostat; Albumin-Bound Paclitaxel; Cyclophosphamide; Doxorubicin; Trastuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators

Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Histone Deacetylase Inhibitors