Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

September 18, 2020 updated by: Joseph Sparano, Albert Einstein College of Medicine

Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel (+/- Trastuzumab) Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Zolinza
Drug: Paclitaxel
Paclitaxel 80 mg/m2 weekly for 12 weeks
Other Names:
  • Taxol
Drug: Trastuzumab
Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose
Other Names:
  • Perception
Drug: Doxorubicin
Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks
Other Names:
  • Adriamycin
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks
Other Names:
  • Cytoxan
Procedure: Surgery
Surgical excision of tumor from breast
Other Names:
  • Mastectomy or lumpectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab
Time Frame: 3 weeks
Dose limiting toxicity in cycle 1
3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albert Einstein College of Medicine

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Joseph Sparano, MD, Montefiore Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

December 13, 2007

First Submitted That Met QC Criteria

December 14, 2007

First Posted (Estimate)

December 17, 2007

Study Record Updates

Last Update Posted (Actual)

October 14, 2020

Last Update Submitted That Met QC Criteria

September 18, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-10-374
  • NYCC1 (Other Identifier: Montefiore Medical Center)
  • NCI-2013-01216 (Registry Identifier: CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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