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

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

Overview[ - collapse ][ - ]

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	Breast Cancer
Intervention	Drug: Vorinostat Drug: Paclitaxel Drug: Trastuzumab Drug: Doxorubicin Drug: Cyclophosphamide Procedure: Mastectomy or Lumpectomy Drug: Post surgery therapy (Trastuzumab)
Phase	Phase 1/Phase 2
Sponsor	Montefiore Medical Center
Responsible Party	Montefiore Medical Center
ClinicalTrials.gov Identifier	NCT00574587
First Received	December 13, 2007
Last Updated	December 14, 2007
Last verified	December 2007

Tracking Information[ + expand ][ + ]

First Received Date	December 13, 2007
Last Updated Date	December 14, 2007
Start Date	December 2007
Estimated Primary Completion Date	January 2010
Current 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]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief Title	Trial for Locally Advanced Her2 Positive Breast Cancer Using Paclitaxel, Trastuzumab, Doxorubicin and Cyclophasmide on a Weekly Basis
Official Title	Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel and Trastuzumab Followed by Doxorubicin-Cyclophosphamide in Patients With Locally Advanced Breast Cancer
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 1/Phase 2
Study Design	Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Breast Cancer
Intervention	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
Study Arm (s)	Experimental: 1

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	54
Estimated Completion Date	January 2010
Estimated Primary Completion Date	Not Provided
Eligibility 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
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Lisa M Escobar-Peralta, BS 718-904-2730 lescobar@montefiore.org
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00574587
Other Study ID Numbers	NYCC1
Has Data Monitoring Committee	Yes
Information Provided By	Montefiore Medical Center
Study Sponsor	Montefiore Medical Center
Collaborators	Merck Sharp & Dohme Corp.
Investigators	Principal Investigator: Joseph Sparano, MD Montefiore Medical Center
Verification Date	December 2007

Locations[ + expand ][ + ]