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

Primary Purpose

Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
vorinostat
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vorinostat)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
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.

Full Information

First Posted
August 16, 2005
Last Updated
March 6, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00132002
Brief Title
Suberoylanilide Hydroxamic Acid in Treating Patients With Progressive Stage IV Breast Cancer
Official Title
Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) as Salvage Therapy in Metastatic Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Terminated
Why Stopped
Early termination for discouraging results
Study Start Date
June 2005 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
January 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (vorinostat)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
vorinostat
Other Intervention Name(s)
L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective Tumor Response Rate
Description
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
Time Frame
Up to 8 weeks
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Estimated using the product-limit method of Kaplan and Meier.
Time Frame
From the initial date of treatment to time of death, up to 5 years.
Title
Progression-free Survival
Description
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.
Time Frame
From start of treatment to the time of documented progression, assessed up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thehang Luu
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

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

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