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

Phase 2

Terminated

• Conditions: Male Breast Cancer; Stage IV Breast Cancer; Recurrent Breast Cancer
• Interventions: Drug: vorinostat; Other: laboratory biomarker analysis

• Registration Number: NCT00132002
• Lead Sponsor: National Cancer Institute (NCI)

Brief 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

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.

Study Timeline

• Study Start: 2005-06
• Study First Submitted: 2005-08-16
• Study First Submitted QC: 2005-08-16
• Study First Posted: 2005-08-19
• Primary Completion: 2008-01
• Study Completion: 2008-01
• Status Verified: 2013-02
• Results First Submitted: 2015-03-06
• Results First Submitted QC: 2015-03-06
• Last Update Submitted: 2015-03-06
• Results First Posted: 2015-03-19
• Last Update Posted: 2015-03-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (vorinostat)	laboratory biomarker analysis	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.
Treatment (vorinostat)	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.

Primary Outcome Measures

Name	Time	Method
Objective Tumor Response Rate	Up to 8 weeks	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

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	From start of treatment to the time of documented progression, assessed up to 5 years	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.
Overall Survival	From the initial date of treatment to time of death, up to 5 years.	Estimated using the product-limit method of Kaplan and Meier.

Trial Locations

Locations (1)

City of Hope; 🇺🇸 Duarte, California, United States