Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

Albert Einstein College of Medicine

Status and phase: Completed; Phase 2; Phase 1

Conditions: Breast Cancer

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00574587

NCI-2013-01216 (Registry Identifier)

07-10-374

NYCC1 (Other Identifier)

Details and patient eligibility

About

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.

Full 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)

Enrollment: 55 patients

Sex: Female

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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55 participants in 1 patient group

Vorinostat Plus Paclitaxel

Experimental group

Description:

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

Treatment:

Procedure: Surgery

Drug: Trastuzumab

Drug: Paclitaxel

Drug: Doxorubicin

Drug: Cyclophosphamide

Drug: Vorinostat