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Vorinostat and Trastuzumab in Treating Patients With Metastatic or Locally Recurrent Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00258349
Recruitment Status : Completed
First Posted : November 24, 2005
Results First Posted : September 27, 2012
Last Update Posted : June 2, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I/II trial is studying the side effects and best dose of vorinostat when given together with trastuzumab and to see how well they work in treating patients with metastatic breast canceror breast cancer that has recurred in the chest wall. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Vorinostat and trastuzumab also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving vorinostat together with trastuzumab may be a better way to block tumor growth.

Condition or disease Intervention/treatment Phase
Breast Cancer Male Breast Cancer Recurrent Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Drug: vorinostat Drug: trastuzumab Phase 1 Phase 2

Detailed Description:


I. To determine the maximum tolerated dose of vorinostat in combination with trastuzumab (Herceptin) in patients with metastatic or local chest wall recurrent HER-2-amplified breast cancer. (Phase I) II. To determine the toxic effects of this regimen in these patients. (Phase I) III. To determine the response rate in patients treated with this regimen. (Phase II)


I. To determine the time to progression in patients treated with this regimen. (Phase II)

OUTLINE: This is an open-label, multicenter, dose-escalation study of vorinostat.

PHASE I: Patients receive oral vorinostat twice daily on days 1-14 and trastuzumab (Herceptin®) IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of vorinostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. At least 6 patients are treated at the MTD.

PHASE II: Patients receive vorinostat at the MTD and trastuzumab as in phase I.

After completion of study treatment, patients are followed periodically for 3 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Trastuzumab (Herceptin) in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Her-2 Amplified Breast Cancer
Study Start Date : August 2006
Actual Primary Completion Date : August 2010
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm I
Patients will receive vorinostat by mouth twice a day for 2 weeks. They will also receive a 90-minute infusion of trastuzumab in week 1.
Drug: vorinostat
Given orally

Drug: trastuzumab
Given IV

Primary Outcome Measures :
  1. Response Rate [ Time Frame: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy ]
    Tumor response is assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Response included complete response (CR) and partial response (PR). CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.

Secondary Outcome Measures :
  1. Time to Progression [ Time Frame: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy ]
    Tumor response is assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Disease progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s). Time to progression is defined as time from registration to disease progression.

  2. Overall Survival [ Time Frame: Survival was assessed every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry ]
    Overall survival is defined as time from registration to death from any cause. Patients who were alive were censored as the last date of known alive.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active or ongoing infection
  • No history of allergic reaction to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin; 1 week for capecitabine) and recovered
  • More than 3 weeks since prior radiotherapy and recovered
  • Recovered from prior therapy
  • At least 2 weeks since prior valproic acid
  • More than 4 weeks since prior investigational agents
  • More than 4 weeks since prior lapatinib ditosylate
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • Measurable disease, defined as >= 1 unidimensionally measurable lesion > 20 mm by conventional techniques or > 10 mm by spiral CT scan
  • No other concurrent investigational agents
  • Concurrent bisphosphonates allowed provided therapy was initiated prior to study treatment
  • No other concurrent anticancer therapy
  • Recurrent or progressive disease while receiving prior trastuzumab (Herceptin) (with or without chemotherapy) OR relapsed within 3 months of last dose of prior adjuvant trastuzumab for metastatic disease
  • Histologically confirmed breast cancer
  • Must overexpress HER-2 gene
  • Metastatic or chest wall recurrent disease
  • Site of measurable disease must not have been irradiated (except chest wall recurrence treated with adjuvant radiation therapy)
  • No untreated brain metastases
  • Previously treated brain metastasis responsive to radiotherapy and/or surgery allowed provided the brain is not the sole site of measurable disease
  • ECOG 0-2
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9 g/dL
  • AST and ALT =< 2 times upper limit of normal
  • Bilirubin =< 1.5 mg/dL (3 mg/dL in the presence of Gilbert's disease provided direct bilirubin is normal)
  • Creatinine =< 1.5 mg/dL
  • LVEF normal by nuclear scan or echocardiogram
  • No evidence of PR prolongation or AV block by EKG
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00258349

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Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Ramona Swaby Eastern Cooperative Oncology Group

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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00258349    
Other Study ID Numbers: NCI-2009-00503
NCI-2009-00503 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E1104 ( Other Identifier: Eastern Cooperative Oncology Group )
E1104 ( Other Identifier: CTEP )
U10CA021115 ( U.S. NIH Grant/Contract )
First Posted: November 24, 2005    Key Record Dates
Results First Posted: September 27, 2012
Last Update Posted: June 2, 2014
Last Verified: October 2013
Additional relevant MeSH terms:
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Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action