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.

Sponsor:

Collaborator:

Merck Sharp & Dohme Corp.

Information provided by (Responsible Party):

Albert Einstein College of Medicine of Yeshiva University

ClinicalTrials.gov Identifier:

NCT00574587

First received: December 13, 2007

Last updated: July 13, 2015

Last verified: July 2015

History of Changes

Purpose

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Paclitaxel Vorinostat Trastuzumab

U.S. FDA Resources

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

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

Eligibility


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00574587

Locations


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.

Investigators


Principal Investigator:	Joseph Sparano, MD	Montefiore Medical Center

More Information


Responsible Party:	Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov 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:


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

ClinicalTrials.gov processed this record on September 27, 2016

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