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

Stage IV Breast Cancer Clinical Trial

Official title:

Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) as Salvage Therapy in Metastatic Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00132002
• Other study ID #: NCI-2012-02836
• Secondary ID: PHII-62N01CM6220
• Status: Terminated
• Phase: Phase 2
• First received: August 16, 2005
• Last updated: March 6, 2015
• Start date: June 2005
• Est. completion date: January 2008

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Male Breast Cancer
• Recurrent Breast Cancer
• Stage IV Breast Cancer

Intervention

Drug:
• vorinostat
Given PO

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Tumor Response Rate	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	Up to 8 weeks	No
Secondary	Overall Survival	Estimated using the product-limit method of Kaplan and Meier.	From the initial date of treatment to time of death, up to 5 years.	No
Secondary	Progression-free Survival	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	From start of treatment to the time of documented progression, assessed up to 5 years	No