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Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00574587
Recruitment Status : Completed
First Posted : December 17, 2007
Results First Posted : September 18, 2020
Last Update Posted : October 14, 2020
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Joseph Sparano, Albert Einstein College of Medicine

Brief Summary:
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 alone (or in combination with plus trastuzumab for HER2-positive disease), and to determine whether vorinostat enhances the effectiveness of standard chemotherapy (+/- trastuzumab) in patients with locally advanced breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Vorinostat Drug: Paclitaxel Drug: Trastuzumab Drug: Doxorubicin Drug: Cyclophosphamide Procedure: Surgery Phase 1 Phase 2

Detailed Description:

This is a phase I-II trial in which patients with stage IIB-IIIC breast cancer will receive:

  1. Neoadjuvant weekly paclitaxel (80 mg/m2 IV weekly x 12 weeks) plus vorinostat (200 or 300 mg PO BID on days 1-3 each paclitaxel dose) and trastuzumab (4 mg/kg loading dose, 2 mg/kg IV weekly x 12 total doses if HER2 positive, followed by:
  2. Doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 2 weeks x 4 cycles (plus G-CSF), followed by:
  3. Surgery (lumpectomy or mastectomy)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel (+/- Trastuzumab) Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer
Study Start Date : December 2007
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Vorinostat Plus Paclitaxel
Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks (and trastuzumab if HER2-positive), followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery
Drug: Vorinostat
Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose
Other Name: Zolinza

Drug: Paclitaxel
Paclitaxel 80 mg/m2 weekly for 12 weeks
Other Name: Taxol

Drug: Trastuzumab
Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Other Name: Perception

Drug: Doxorubicin
Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Other Name: Adriamycin

Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Other Name: Cytoxan

Procedure: Surgery
Surgical excision of tumor from breast
Other Name: Mastectomy or lumpectomy

Primary Outcome Measures :
  1. Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab [ Time Frame: 3 weeks ]
    Dose limiting toxicity in cycle 1

Secondary Outcome Measures :
  1. Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer. [ Time Frame: 6 months ]
    Pathological Complete Response (CR) defined as absence of invasive cancer at surgery

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes 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

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 identifier (NCT number): NCT00574587

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United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
Sponsors and Collaborators
Albert Einstein College of Medicine
Merck Sharp & Dohme LLC
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Principal Investigator: Joseph Sparano, MD Montefiore Medical Center
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Responsible Party: Joseph Sparano, Professor, Oncology, Albert Einstein College of Medicine Identifier: NCT00574587    
Other Study ID Numbers: 07-10-374
NYCC1 ( Other Identifier: Montefiore Medical Center )
NCI-2013-01216 ( Registry Identifier: CTRP )
First Posted: December 17, 2007    Key Record Dates
Results First Posted: September 18, 2020
Last Update Posted: October 14, 2020
Last Verified: September 2020
Keywords provided by Joseph Sparano, Albert Einstein College of Medicine:
Neoadjuvant Chemotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
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
Antineoplastic Agents, Immunological
Histone Deacetylase Inhibitors