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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00132002
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.5

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer	Drug: vorinostat; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) as Salvage Therapy in Metastatic Breast Cancer
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Thehang Luu, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00132002
• Other Study ID Numbers: NCI-2012-02836; PHII-62; N01CM62209; CDR0000438776
• First Posted: Aug 19, 2005
• Last Update Posted: Mar 19, 2015
• Last Verified: Feb 1, 2013

• Additional relevant MeSH terms: Breast Neoplasms; Breast Neoplasms, Male; Vorinostat

Study Results

Participant Flow

Arm/Group Title	Arm 1
Arm/Group Description	Vorinostat, 200 mg orally twice daily, was administered for the first 14 days of each 21 day cycle. Treatment was continued unless either disease progression was determined, the patient requested to be withdrawn from the study, or excessive toxicity was noted.
Period Title: Overall Study
STARTED	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm 1
Arm/Group Description	Vorinostat, 200 mg orally twice daily, was administered for the first 14 days of each 21 day cycle. Treatment was continued unless either disease progression was determined, the patient requested to be withdrawn from the study, or excessive toxicity was noted.
Overall Participants	14
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	14 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Vorinostat, 200 mg orally twice daily, was administered for the first 14 days of each 21 day cycle. Treatment was continued unless either disease progression was determined, the patient requested to be withdrawn from the study, or excessive toxicity was noted.
Measure Participants	14
Number [percentage of participants]	0 0%

2. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Vorinostat, 200 mg orally twice daily, was administered for the first 14 days of each 21 day cycle. Treatment was continued unless either disease progression was determined, the patient requested to be withdrawn from the study, or excessive toxicity was noted.
Measure Participants	14
Median (95% Confidence Interval) [Months]	24

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Vorinostat, 200 mg orally twice daily, was administered for the first 14 days of each 21 day cycle. Treatment was continued unless either disease progression was determined, the patient requested to be withdrawn from the study, or excessive toxicity was noted.
Measure Participants	14
Median (95% Confidence Interval) [Months]	2.6

Adverse Events

Time Frame	Adverse events occured over a period of 1 year and 7 months.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Arm 1
Arm/Group Description	Vorinostat, 200 mg orally twice daily, was administered for the first 14 days of each 21 day cycle. Treatment was continued unless either disease progression was determined, the patient requested to be withdrawn from the study, or excessive toxicity was noted.
All Cause Mortality
	Arm 1
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm 1
	Affected / at Risk (%)	# Events
Total	3/14 (21.4%)
General disorders
Disease progression	2/14 (14.3%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Arm 1
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	9/14 (64.3%)	20
Gastrointestinal disorders
Constipation	4/14 (28.6%)	9
Diarrhea	6/14 (42.9%)	12
Dry mouth	2/14 (14.3%)	2
Ear, nose and throat examination abnormal	2/14 (14.3%)	3
Mucositis oral	3/14 (21.4%)	5
Nausea	12/14 (85.7%)	32
Vomiting	7/14 (50%)	7
General disorders
Edema limbs	2/14 (14.3%)	2
Fatigue	11/14 (78.6%)	29
Pain	3/14 (21.4%)	3
Investigations
Alanine aminotransferase increased	4/14 (28.6%)	6
Alkaline phosphatase increased	6/14 (42.9%)	10
Aspartate aminotransferase increased	12/14 (85.7%)	38
Creatinine increased	3/14 (21.4%)	5
Hyperbilirubinemia	2/14 (14.3%)	2
Leukopenia	6/14 (42.9%)	15
Lymphopenia	10/14 (71.4%)	26
Platelet count decreased	6/14 (42.9%)	11
Weight loss	2/14 (14.3%)	2
Metabolism and nutrition disorders
Anorexia	3/14 (21.4%)	3
Hypercalcemia	2/14 (14.3%)	2
Hyperglycemia	8/14 (57.1%)	13
Hypermagnesemia	2/14 (14.3%)	2
Hypernatremia	1/14 (7.1%)	1
Hypertriglyceridemia	1/14 (7.1%)	1
Hypoalbuminemia	9/14 (64.3%)	22
Hypocalcemia	2/14 (14.3%)	2
Hypoglycemia	3/14 (21.4%)	8
Hypokalemia	4/14 (28.6%)	5
Hyponatremia	4/14 (28.6%)	6
Hypophosphatemia	3/14 (21.4%)	3
Serum phosphate decreased	1/14 (7.1%)	1
Serum potassium decreased	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/14 (7.1%)	1
Back pain	1/14 (7.1%)	1
Bone pain	3/14 (21.4%)	8
Joint pain	3/14 (21.4%)	4
Myalgia	3/14 (21.4%)	3
Neck pain	1/14 (7.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	2/14 (14.3%)	2
Nervous system disorders
Headache	1/14 (7.1%)	1
Peripheral sensory neuropathy	2/14 (14.3%)	4
Speech disorder	1/14 (7.1%)	1
Psychiatric disorders
Anxiety	3/14 (21.4%)	3
Depression	1/14 (7.1%)	1
Insomnia	1/14 (7.1%)	3
Renal and urinary disorders
Bladder pain	1/14 (7.1%)	2
Proteinuria	1/14 (7.1%)	1
Urinary frequency	1/14 (7.1%)	1
Urinary retention	1/14 (7.1%)	2
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/14 (14.3%)	2
Aspiration	1/14 (7.1%)	1
Cough	2/14 (14.3%)	6
Dyspnea	3/14 (21.4%)	6
Pleural effusion	1/14 (7.1%)	1
Respiratory disorder	3/14 (21.4%)	5
Voice alteration	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/14 (14.3%)	4
Dry skin	3/14 (21.4%)	4
Pruritus	1/14 (7.1%)	1
Rash desquamating	1/14 (7.1%)	2
Skin disorder	1/14 (7.1%)	1
Vascular disorders
Hypertension	1/14 (7.1%)	1

Limitations/Caveats

Study was terminated early after the first stage of a two-stage design, allowing for early termination for discouraging results

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.