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

NCT00262834 | Completed Phase 2 Results

• 6 other identifiers: NCI-2009-00098CDR0000445404SKCCC J05046914U01CA070095P30CA006973
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Change in Tissue Histone Acetylation After 3 Days of Treatment

  Baseline and after 3 day of Vorinostat

• Change in Blood (Peripheral Blood Mononuclear Cells) Histone Acetylation After 3 Days of Treatment

  Baseline and after 3 day of Vorinostat

Study Arms (1)

Arm I

EXPERIMENTAL

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; Other: conventional surgery

Interventions

vorinostat DRUG

Given orally, conventional surgery to follow.

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

conventional surgery OTHER

Undergo conventional surgery

Also known as: surgery, conventional

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vorinostat; Surgical Procedures, Operative; Congresses as Topic

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Organizations; Health Care Economics and Organizations

Limitations and Caveats

The main limitation of the trial is the unexpectedly low proportion of matched evaluable samples available for the biomarkers studied, ranging from 44% to 92%.

Results Point of Contact

• Title: Vered Stearns
• Organization: SKCCC

vstearn1@jhmi.edu

4432876489

Study Officials

• Vered Stearns

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Patients receive oral vorinostat twice daily on days -3 to 0. Approximately 2 hours after the final dose of vorinostat, patients undergo conventional surgical resection of the tumor on day 0. After completion of study treatment, patients are followed for 30 days.

Study Record Dates

• First Submitted: December 6, 2005
• First Posted: December 7, 2005
• Study Start: October 1, 2005
• Primary Completion: October 1, 2008
• Study Completion: May 1, 2013
• Last Updated: February 19, 2020
• Results First Posted: September 8, 2014

Record last verified: 2020-02

Locations

US (1)