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A Phase I/II 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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer

Thank you

Trial Information

A Phase I/II 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


OBJECTIVES:

Primary

- Determine the maximum tolerated dose (MTD) of vorinostat in combination with
trastuzumab (Herceptin^®) in patients with metastatic or local chest wall recurrent
HER-2-amplified breast cancer. (Phase I)

- Determine the toxic effects of this regimen in these patients. (Phase I)

- Determine the response rate in patients treated with this regimen. (Phase II)

Secondary

- 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^®) intravenously (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.

ACTUAL ACCRUAL: a total of 16 patients enrolled on the study.

Inclusion Criteria


INCLUSION CRITERIA:

- Histologically confirmed breast cancer

- Must overexpress human epidermal growth factor receptor II (HER-2) gene

- Metastatic or chest wall recurrent disease

- 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

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by
conventional techniques or > 10 mm by spiral computed tomography (CT) scan

- 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

- Male or female

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Adequate organ function:

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (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

- Left ventricular ejection fraction (LVEF) normal by nuclear scan or echocardiogram

- Negative pregnancy test

- Fertile patients must use effective contraception

- 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

- Concurrent bisphosphonates allowed provided therapy was initiated prior to study
treatment

EXCLUSION CRITERIA:

- Evidence of PR prolongation or atrioventricular (AV) block by Electrocardiography
(EKG)

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Concurrent radiotherapy for brain metastases

- Concurrent combination antiretroviral therapy for HIV-positive patients

- Other concurrent investigational agents

- Other concurrent anticancer therapy

- Active or ongoing infection

- History of allergic reaction to compounds of similar chemical or biologic composition
to vorinostat or other agents used in study

- Psychiatric illness or social situation that would preclude study compliance

- Other uncontrolled illness

- Pregnant or nursing

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Response Rate

Outcome 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.

Outcome 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

Safety Issue:

No

Principal Investigator

Ramona Swaby, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00503

NCT ID:

NCT00258349

Start Date:

August 2006

Completion Date:

September 2010

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • male breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • Breast Neoplasms

Name

Location

CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Meeker County Memorial HospitalLichfield, Minnesota  55355
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
HealthEast Cancer Care at St. Joseph's HospitalSt Paul, Minnesota  55102
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
HealthEast Cancer Care at Woodwinds Health CampusWoodbury, Minnesota  55125
St. Rita's Medical CenterLima, Ohio  45801
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
Our Lady of Mercy Medical Center Comprehensive Cancer CenterBronx, New York  10466
St. Vincent's Comprehensive Cancer Center - ManhattanNew York, New York  10011
Lewistown HospitalLewistown, Pennsylvania  17044
Mount Nittany Medical CenterState College, Pennsylvania  16803
MBCCOP - Medical College of Georgia Cancer CenterAugusta, Georgia  30912-3730
Swedish-American Regional Cancer CenterRockford, Illinois  61104-2315
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Mercy Capitol HospitalDes Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Lurleen Wallace Comprehensive Cancer at University of Alabama - BirminghamBirmingham, Alabama  35294