Conditions: Breast Cancer
Keywords: Vorinostat Neoadjuvant Chemotherapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 55
Healthy volunteers: no

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.

Detailed 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)

Arms:
arm 1: 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

Interventions: intervention 1: Vorinostat intervention 2: Paclitaxel intervention 3: Trastuzumab intervention 4: Doxorubicin intervention 5: Cyclophosphamide intervention 6: Surgery
Intervention descriptions: intervention 1: Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose intervention 2: Paclitaxel 80 mg/m2 weekly for 12 weeks intervention 3: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose intervention 4: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks intervention 5: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks intervention 6: Surgical excision of tumor from breast

Protocol document: