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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00258349
• Other study ID #: NCI-2009-00503
• Secondary ID: NCI-2009-00503CD
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 22, 2005
• Last updated: May 29, 2014
• Start date: August 2006
• Est. completion date: September 2010

Study information

• Verified date: October 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Breast Neoplasms, Male
• Male Breast Cancer
• Recurrent Breast Cancer
• Stage IIIB Breast Cancer
• Stage IIIC Breast Cancer
• Stage IV Breast Cancer

Intervention

Drug:
• vorinostat
Given orally
• trastuzumab
Given IV

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Eastern Cooperative Oncology Group	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa Oncology Research Association CCOP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Saint Vincent's Hospital and Medical Center of New York	New York	New York
United States	Regions Hospital	Saint Paul	Minnesota
United States	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Woodwinds Health Campus	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy	No
Secondary	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.	Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy	No
Secondary	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.	Survival was assessed every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry	No