Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy

• ClinicalTrials.gov Identifier: NCT00574587
• Recruitment Status: Completed
• First Posted: December 17, 2007
• Results First Posted: September 18, 2020
• Last Update Posted: October 14, 2020
• Sponsor: Albert Einstein College of Medicine
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Joseph Sparano, Albert Einstein College of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Vorinostat; Drug: Paclitaxel; Drug: Trastuzumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Procedure: Surgery	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I-II Trial of Vorinostat Plus Weekly Paclitaxel (+/- Trastuzumab) Followed by Doxorubicin-cyclophosphamide in Patients With Locally Advanced Breast Cancer
• Study Start Date: December 2007
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: Vorinostat Plus 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

Drug: Vorinostat; Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose; Other Name: Zolinza; Drug: Paclitaxel; Paclitaxel 80 mg/m2 weekly for 12 weeks; Other Name: Taxol; Drug: Trastuzumab; Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose; Other Name: Perception; Drug: Doxorubicin; Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks; Other Name: Adriamycin; Drug: Cyclophosphamide; Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks; Other Name: Cytoxan; Procedure: Surgery; Surgical excision of tumor from breast; Other Name: Mastectomy or lumpectomy

Outcome Measures

Primary Outcome Measures :

1. Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab [ Time Frame: 3 weeks ]
   Dose limiting toxicity in cycle 1

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10461

Sponsors and Collaborators

Albert Einstein College of Medicine

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Joseph Sparano, MD; Montefiore Medical Center

More Information

• Responsible Party: Joseph Sparano, Professor, Oncology, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT00574587
• Other Study ID Numbers: 07-10-374; NYCC1 ( Other Identifier: Montefiore Medical Center ); NCI-2013-01216 ( Registry Identifier: CTRP )
• First Posted: December 17, 2007
• Results First Posted: September 18, 2020
• Last Update Posted: October 14, 2020
• Last Verified: September 2020

Keywords provided by Joseph Sparano, Albert Einstein College of Medicine:

Vorinostat; Neoadjuvant Chemotherapy

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Cyclophosphamide; Doxorubicin; Trastuzumab; Vorinostat; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antineoplastic Agents, Immunological; Histone Deacetylase Inhibitors