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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
Not Enrolling
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



- 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)


- 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


- 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


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

- 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:


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:


Principal Investigator

Ramona Swaby, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fox Chase Cancer Center


United States: Food and Drug Administration

Study ID:




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



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