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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2007 by Montefiore Medical Center.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT00574587
First received: December 13, 2007
Last updated: December 14, 2007
Last verified: December 2007
  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:


Further study details as provided by Montefiore Medical Center:

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 2010
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
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

Contacts
Contact: Lisa M Escobar-Peralta, BS 718-904-2730 lescobar@montefiore.org

Locations
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Contact: Lisa M Escobar, BS    718-904-2730    lescobar@montefiore.org   
Principal Investigator: Joseph Sparano, MD         
Sponsors and Collaborators
Montefiore Medical Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Joseph Sparano, MD Montefiore Medical Center
  More Information

No publications provided

Responsible Party: Joseph Sparano, MD, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT00574587     History of Changes
Other Study ID Numbers: NYCC1, 07-10-374
Study First Received: December 13, 2007
Last Updated: December 14, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by Montefiore Medical Center:
Vorinostat
Neoadjuvant Chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Liposomal doxorubicin
Trastuzumab
Vorinostat
Doxorubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 28, 2014