Vorinostat in Treating Women Who Are Undergoing Surgery For Newly Diagnosed Stage I, Stage II, or Stage III Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00262834
First received: December 6, 2005
Last updated: August 28, 2014
Last verified: June 2014
  Purpose

This phase II trial is studying how well vorinostat works in treating women who are undergoing surgery for newly diagnosed stage I, stage II, or stage III breast cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may shrink the tumor so that it can be removed.


Condition Intervention
Breast Cancer
Stage I Breast Cancer
Stage II Breast Cancer
Stage III Breast Cancer
Drug: vorinostat
Other: conventional surgery

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study Evaluating Surrogates of Response to Short Term Oral Suberoylanilide Hydroxamic Acid (SAHA) in Women With Newly Diagnosed Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: After 3 days of vorinostat ] [ Designated as safety issue: Yes ]
    Participants were evaluated for adverse events due to vorinostat to assess if it was safe to give the drug prior to surgery. 17 of 25 participants who received vorinostat experienced at least 1 adverse event believed to be related to the study drug; no adverse events were severe, and the treatment was considered safe.

  • Change in Tissue Proliferation After 3 Days of Treatment [ Time Frame: After 3 days of vorinostat ] [ Designated as safety issue: No ]
    Change in Ki-67 (a marker of tissue proliferation) by IHC compared to baseline in the treated (22 evaluable samples) or untreated patients (15 evaluable samples) were analyzed between groups. Ki-67 is a protein in cells that increases as cellsprepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells.

  • Change in Tissue Apoptosis After 3 Days of Treatment [ Time Frame: Baseline and after 3 day of vorinostat ] [ Designated as safety issue: No ]
    Change in cleaved caspase-3 (a marker of tissue apoptosis) by IHC compared to baseline in the treated (19 evaluable samples) or untreated patients (12 evaluable samples) were analyzed between groups. Cleaved caspase-3 is a protein in cells involved in apoptosis (cell death).


Secondary Outcome Measures:
  • Change in Tissue Histone Acetylation After 3 Days of Treatment [ Time Frame: Baseline and after 3 day of Vorinostat ] [ Designated as safety issue: No ]
  • Change in Blood (Peripheral Blood Mononuclear Cells) Histone Acetylation After 3 Days of Treatment [ Time Frame: Baseline and after 3 day of Vorinostat ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: October 2005
Study Completion Date: May 2013
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Patients receive oral vorinostat twice daily on days -3 to 0. Approximately 2 hours after the final dose of vorinostat, patients undergo surgical resection of the tumor on day 0.

After completion of study treatment, patients are followed for 30 days.

Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: conventional surgery
Undergo surgery
Other Name: surgery, conventional

Detailed Description:

PRIMARY OBJECTIVE:

I. Determine the safety and tolerability of vorinostat in women undergoing surgery for newly diagnosed stage I-III breast cancer.

OULINE: This is a multicenter, pilot study.

Patients receive oral vorinostat twice daily on days -3 to 0. Approximately 2 hours after the final dose of vorinostat, patients undergo surgical resection of the tumor on day 0.

After completion of study treatment, patients are followed for 30 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • No prior or concurrent hormonal therapy for breast cancer
  • Histologically confirmed breast cancer, stage I-III disease, scheduled to undergo definitive surgery or other primary treatment (e.g., preoperative/neoadjuvant systemic treatment) for breast cancer
  • ECOG 0-2 OR Karnofsky 60-100%
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • PT ≤ 14 seconds
  • Creatinine normal
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled intercurrent illness
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to vorinostat
  • At least 30 days since prior hormone replacement therapy (e.g., estrogen and/or progestin)
  • Concurrent vaginal hormone preparations (e.g., vagifem or estring) allowed
  • No concurrent birth control pills
  • No prior radiotherapy to the ipsilateral breast
  • No prior or concurrent radiotherapy for breast cancer
  • No prior or concurrent novel therapy for breast cancer
  • At least 14 days since prior valproic acid or another histone deacetylase inhibitor
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent therapy for this cancer
  • WBC ≥ 3,000/mm^3
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262834

Locations
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Investigators
Principal Investigator: Vered Stearns Johns Hopkins University/Sidney Kimmel Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00262834     History of Changes
Other Study ID Numbers: NCI-2009-00098, NCI-2009-00098, CDR0000445404, SKCCC J0504, 6914, U01CA070095, P30CA006973
Study First Received: December 6, 2005
Results First Received: July 10, 2013
Last Updated: August 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014