Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

November 22, 2005
May 29, 2014
August 2006
August 2010   (final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00258349 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
Vorinostat and Trastuzumab in Treating Patients With Metastatic or Locally Recurrent Breast Cancer
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

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Drug: vorinostat
    Given orally
  • Drug: trastuzumab
    Given IV
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.
Interventions:
  • Drug: vorinostat
  • Drug: trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
September 2010
August 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00258349
NCI-2009-00503, NCI-2009-00503, CDR0000449963, E1104, E1104, U10CA021115
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Ramona Swaby Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP