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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00258349
First received: November 22, 2005
Last updated: May 29, 2014
Last verified: October 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 16
Study Start Date: August 2006
Study Completion Date: September 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVE:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00258349

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Iowa
Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316
Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Iowa Oncology Research Association CCOP
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates
Des Moines, Iowa, United States, 50314
Mercy Capitol
Des Moines, Iowa, United States, 50307
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Mercy Medical Center-Sioux City
Sioux City, Iowa, United States, 51104
Saint Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
Siouxland Hematology Oncology Associates
Sioux City, Iowa, United States, 51101
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
United States, Minnesota
Hutchinson Area Health Care
Hutchinson, Minnesota, United States, 55350
Meeker County Memorial Hospital
Litchfield, Minnesota, United States, 55355
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States, 55109
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States, 55407
Regions Hospital
Saint Paul, Minnesota, United States, 55101
Saint Joseph's Hospital - Healtheast
Saint Paul, Minnesota, United States, 55102
Saint Francis Regional Medical Center
Shakopee, Minnesota, United States, 55379
Woodwinds Health Campus
Woodbury, Minnesota, United States, 55125
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Saint Vincent's Hospital and Medical Center of New York
New York, New York, United States, 10011
Sponsors and Collaborators
Investigators
Principal Investigator: Ramona Swaby Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00258349     History of Changes
Other Study ID Numbers: NCI-2009-00503, NCI-2009-00503, CDR0000449963, E1104, E1104, U10CA021115
Study First Received: November 22, 2005
Results First Received: August 28, 2012
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms, Male
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Vorinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014