Suberoylanilide Hydroxamic Acid in Treating Patients With Progressive Stage IV Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00132002
First received: August 16, 2005
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

This phase II trial is studying how well suberoylanilide hydroxamic acid works in treating patients with progressive stage IV breast cancer. Drugs used in chemotherapy, such as suberoylanilide hydroxamic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Suberoylanilide hydroxamic acid may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth


Condition Intervention Phase
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: vorinostat
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) as Salvage Therapy in Metastatic Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective tumor response rate according to the RECIST criteria [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    Response rates (RECIST) will be calculated as the percent of treated patients whose best response is a CR or PR, and exact 95% confidence intervals will be calculated for this estimate (reflecting the interim analysis).


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Time to progression [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Toxicity profile using the NCI CTCAE 3.0 scale [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: Yes ]
    At the completion of the study, all toxicities will be summarized and reported. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.


Enrollment: 37
Study Start Date: June 2005
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat)
Patients receive oral suberoylanilide hydroxamic acid twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the response rate in patients receiving SAHA for stage IV breast cancer.

SECONDARY OBJECTIVES:

I. Time to progression. II. Overall survival. III. Toxicity profile. IV. Assessment of potential biological correlates.

OUTLINE: This is a multicenter study.

Patients receive oral suberoylanilide hydroxamic acid twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 8 weeks.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed stage IV adenocarcinoma of the breast; tumor blocks and/or slides from original diagnosis or metastatic work-up must be available for correlative studies
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan
  • Prior adjuvant therapy, and up to 2 lines of prior chemotherapy (including trastuzumab containing regimens in Her-2 positive patients) for metastatic disease are allowed; prior radiation therapy is allowed, prior hormonal therapy is allowed
  • Life expectancy of greater than 6 months
  • Performance status: ECOG 0- 2
  • Absolute neutrophil count >= 1,000/μl
  • Platelets >= 100,000/μl
  • Serum creatinine =< 1.6 mg/dl or calculated measured clearance >= 60 cc/min
  • Total bilirubin =< 2 mg/dL
  • AST and ALT =< 3 times institutional upper normal level
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of SAHA will be determined following review by the Principal Investigator
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients should not have taken valproic acid for at least two weeks prior to study entry

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases are excluded from this clinical trial unless the metastases are controlled after therapy and have not been treated with steroids within the past two months
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA; these compounds include sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because SAHA is a HDAC inhibitor agent with an unknown potential for teratogenesis; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SAHA, breastfeeding should be discontinued if the mother is treated with SAHA
  • HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SAHA
  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: NCT00132002

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Thehang Luu Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00132002     History of Changes
Other Study ID Numbers: NCI-2012-02836, PHII-62, N01CM62209, CDR0000438776
Study First Received: August 16, 2005
Last Updated: February 26, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 18, 2014