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

A Pilot Study Evaluating Surrogates of Response to Short Term Oral Suberoylanilide Hydroxamic Acid (SAHA) in Women With Newly Diagnosed Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer
• Intervention / Treatment: Drug: vorinostat; Other: conventional surgery

Detailed Description

PRIMARY OBJECTIVE:

I. Determine the safety and tolerability of vorinostat in women undergoing conventional 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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Exclusion criteria:

• Patients must not be recieving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA.
• Patients may not be taking valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to initiating SAHA.
• Women who are pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 conventional surgery of the tumor on day 0. After completion of study treatment, patients are followed for 30 days.	Drug: vorinostat; Given orally, conventional surgery to follow.; Other Names: SAHA; Zolinza; L-001079038; suberoylanilide hydroxamic acid; Other: conventional surgery; Undergo conventional surgery; Other Names: surgery, conventional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	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.	After 3 days of vorinostat
Change in Tissue Proliferation After 3 Days of Treatment	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.	After 3 days of vorinostat
Change in Tissue Apoptosis After 3 Days of Treatment	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).	Baseline and after 3 day of vorinostat

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tissue Histone Acetylation After 3 Days of Treatment	To evaluate change from baseline in tissue histone acetylation in patients with primary breast cancer who received three days of Short Term Oral Suberoylanilide Hydroxamic Acid (SAHA) 300 mg PO bid immediately prior to definitive breast surgery or other primary treatment. This is measured by Cumulative Methylation Index, which is reported as the sum of all %M for all genes. %M= (methylated copies divided by methylated + unmethylated copies) x 100.	Baseline and after 3 day of Vorinostat
Change in Blood (Peripheral Blood Mononuclear Cells) Histone Acetylation After 3 Days of Treatment	To evaluate baseline and change in histone acetylation in polymononuclear cells in patients with primary breast cancer who received three days of SAHA 300 mg PO bid immediately prior to definitive breast surgery or other primary treatment.	Baseline and after 3 day of Vorinostat

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vered Stearns, Johns Hopkins University/Sidney Kimmel Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: December 6, 2005
• First Submitted That Met QC Criteria: December 6, 2005
• First Posted (Estimate): December 7, 2005

Study Record Updates

• Last Update Posted (Actual): February 19, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: NCI-2009-00098 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA006973 (U.S. NIH Grant/Contract); U01CA070095 (U.S. NIH Grant/Contract); 6914 (Other Identifier: CTEP); CDR0000445404 (Other Identifier: Clinical Data Repository (CT.gov)); SKCCC J0504 (Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center)