Trial for Locally Advanced Her2 Positive Breast Cancer Using Paclitaxel, Trastuzumab, Doxorubicin and Cyclophasmide on a Weekly Basis
Recruitment status was Recruiting
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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 |
- To determine the recommended phase II dose of vorinostat in combination with weekly paclitaxel/trastuzumab [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- 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 |
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| Contact: Lisa M Escobar-Peralta, BS | 718-904-2730 | lescobar@montefiore.org |
| 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 | |
| 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 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 Tubulin Modulators Antimitotic Agents Mitosis Modulators Antineoplastic Agents, Phytogenic Histone Deacetylase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013