Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

Phase 1

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Vorinostat; Drug: Paclitaxel; Drug: Trastuzumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Procedure: Surgery

• Registration Number: NCT00574587
• Lead Sponsor: Albert Einstein College of Medicine

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)

Study Timeline

• Study Start: 2007-12
• Study First Submitted: 2007-12-13
• Study First Submitted QC: 2007-12-14
• Study First Posted: 2007-12-17
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2020-03-30
• Results First Submitted QC: 2020-08-29
• Status Verified: 2020-09
• Results First Posted: 2020-09-18
• Last Update Submitted: 2020-09-18
• Last Update Posted: 2020-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 55

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

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Exclusion Criteria

• May not be receiving any other investigational agents
• Uncontrolled intercurrent illness

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vorinostat Plus Paclitaxel	Surgery	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
Vorinostat Plus Paclitaxel	Vorinostat	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
Vorinostat Plus Paclitaxel	Paclitaxel	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
Vorinostat Plus Paclitaxel	Trastuzumab	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
Vorinostat Plus Paclitaxel	Doxorubicin	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
Vorinostat Plus Paclitaxel	Cyclophosphamide	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

Primary Outcome Measures

Name	Time	Method
Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab	3 weeks	Dose limiting toxicity in cycle 1

Secondary Outcome Measures

Name	Time	Method
Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer.	6 months	Pathological Complete Response (CR) defined as absence of invasive cancer at surgery

Trial Locations

Locations (1)

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States