Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Temporarily closed	18 and over	NCI, Other	CDR0000449963 ECOG-E1104, NCT00258349

Trial Description

Summary

RATIONALE: 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.

PURPOSE: 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.

Further Study Information

OBJECTIVES:

Primary

• 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)

• 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^®) 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

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Must overexpress 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 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

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

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

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9 g/dL

Hepatic

• 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)

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• 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

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin; 1 week for capecitabine) and recovered

Radiotherapy

• See Disease Characteristics

• More than 3 weeks since prior radiotherapy and recovered

• No concurrent radiotherapy for brain metastases

Surgery

• See Disease Characteristics

Other

• 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

• No other concurrent investigational agents

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

• No other concurrent anticancer therapy

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Ramona Swaby

Study Chair

Joseph A. Sparano

Lori J. Goldstein

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00258349
Information obtained from ClinicalTrials.gov on December 03, 2009

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