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

Primary Purpose

Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
vorinostat
trastuzumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

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

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

Sites / Locations

  • University of Alabama at Birmingham
  • Mercy Capitol
  • Iowa Methodist Medical Center
  • Iowa Oncology Research Association CCOP
  • Medical Oncology and Hematology Associates-Des Moines
  • Medical Oncology and Hematology Associates
  • Mercy Medical Center - Des Moines
  • Iowa Lutheran Hospital
  • Siouxland Hematology Oncology Associates
  • Mercy Medical Center-Sioux City
  • Saint Luke's Regional Medical Center
  • Johns Hopkins University
  • Eastern Cooperative Oncology Group
  • Hutchinson Area Health Care
  • Meeker County Memorial Hospital
  • Saint John's Hospital - Healtheast
  • Virginia Piper Cancer Institute
  • Hennepin County Medical Center
  • Regions Hospital
  • Saint Joseph's Hospital - Healtheast
  • Saint Francis Regional Medical Center
  • Woodwinds Health Campus
  • Albert Einstein College of Medicine
  • Montefiore Medical Center
  • Saint Vincent's Hospital and Medical Center of New York

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

Response Rate
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
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
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.

Full Information

First Posted
November 22, 2005
Last Updated
May 29, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00258349
Brief Title
Vorinostat and Trastuzumab in Treating Patients With Metastatic or Locally Recurrent Breast Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
September 2010 (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 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.
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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
vorinostat
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
trastuzumab
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Response Rate
Description
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.
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
Secondary Outcome Measure Information:
Title
Time to Progression
Description
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.
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
Title
Overall Survival
Description
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ramona Swaby
Organizational Affiliation
Eastern Cooperative Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Mercy Capitol
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50307
Country
United States
Facility Name
Iowa Methodist Medical Center
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
Iowa Oncology Research Association CCOP
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
Medical Oncology and Hematology Associates-Des Moines
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
Medical Oncology and Hematology Associates
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
Mercy Medical Center - Des Moines
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
Iowa Lutheran Hospital
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50316
Country
United States
Facility Name
Siouxland Hematology Oncology Associates
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
Facility Name
Mercy Medical Center-Sioux City
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51104
Country
United States
Facility Name
Saint Luke's Regional Medical Center
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51104
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8936
Country
United States
Facility Name
Eastern Cooperative Oncology Group
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hutchinson Area Health Care
City
Hutchinson
State/Province
Minnesota
ZIP/Postal Code
55350
Country
United States
Facility Name
Meeker County Memorial Hospital
City
Litchfield
State/Province
Minnesota
ZIP/Postal Code
55355
Country
United States
Facility Name
Saint John's Hospital - Healtheast
City
Maplewood
State/Province
Minnesota
ZIP/Postal Code
55109
Country
United States
Facility Name
Virginia Piper Cancer Institute
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Saint Joseph's Hospital - Healtheast
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Saint Francis Regional Medical Center
City
Shakopee
State/Province
Minnesota
ZIP/Postal Code
55379
Country
United States
Facility Name
Woodwinds Health Campus
City
Woodbury
State/Province
Minnesota
ZIP/Postal Code
55125
Country
United States
Facility Name
Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States
Facility Name
Saint Vincent's Hospital and Medical Center of New York
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States

12. IPD Sharing Statement

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

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