Clinical trial NCT00258349: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-11-24
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response Rate
timeFrame: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy
Secondary outcomes:
measure: Time to Progression
timeFrame: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy
measure: Overall Survival
timeFrame: Survival was assessed every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Des Moines
country: United States
facility: Mercy Capitol
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Eastern Cooperative Oncology Group
state: Massachusetts
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Litchfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Saint Joseph's Hospital - Healtheast
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Woodwinds Health Campus
state: Minnesota
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Saint Vincent's Hospital and Medical Center of New York
state: New York
Study officials:
affiliation: Eastern Cooperative Oncology Group
name: Ramona Swaby
role: PRINCIPAL_INVESTIGATOR
References: