Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

NCT00574587 | Completed Phase 1 Results DMC

• 3 other identifiers: 07-10-374NYCC1NCI-2013-01216
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Vorinostat; Neoadjuvant Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab

  Dose limiting toxicity in cycle 1

  3 weeks

Secondary Outcomes (1)

• Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer.

  6 months

Study Arms (1)

Vorinostat Plus Paclitaxel

EXPERIMENTAL

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; Drug: Paclitaxel; Drug: Trastuzumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Procedure: Surgery

Interventions

Vorinostat DRUG

Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose

Also known as: Zolinza

Vorinostat Plus Paclitaxel

Paclitaxel DRUG

Paclitaxel 80 mg/m2 weekly for 12 weeks

Also known as: Taxol

Vorinostat Plus Paclitaxel

Trastuzumab DRUG

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

Also known as: Perception

Vorinostat Plus Paclitaxel

Doxorubicin DRUG

Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks

Also known as: Adriamycin

Vorinostat Plus Paclitaxel

Cyclophosphamide DRUG

Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks

Also known as: Cytoxan

Vorinostat Plus Paclitaxel

Surgery PROCEDURE

Surgical excision of tumor from breast

Also known as: Mastectomy or lumpectomy

Vorinostat Plus Paclitaxel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• May not be receiving any other investigational agents
• Uncontrolled intercurrent illness

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vorinostat; Paclitaxel; Trastuzumab; Doxorubicin; Cyclophosphamide; Surgical Procedures, Operative; Mastectomy; Mastectomy, Segmental

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Markenya Mirander
• Organization: Montefiore Medical Center

MMIRANDE@montefiore.org

718-862-8840

Study Officials

• Joseph Sparano, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Oncology

Study Record Dates

• First Submitted: December 13, 2007
• First Posted: December 17, 2007
• Study Start: December 1, 2007
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 14, 2020
• Results First Posted: September 18, 2020

Record last verified: 2020-09

Locations

US (1)