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

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ClinicalTrials.gov Identifier: NCT00574587

Recruitment Status : Unknown

Verified July 2015 by Albert Einstein College of Medicine, Inc..
Recruitment status was: Active, not recruiting

First Posted : December 17, 2007

Last Update Posted : July 14, 2015

Sponsor:

Collaborator:

Merck Sharp & Dohme Corp.

Information provided by (Responsible Party):

Albert Einstein College of Medicine, Inc.

Study Description

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


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

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Doxorubicin Paclitaxel Vorinostat Trastuzumab

U.S. FDA Resources

Arms and Interventions

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

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

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574587

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


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 Key Record Dates
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

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