Vorinostat and Trastuzumab in Treating Patients With Metastatic or Locally Recurrent Breast Cancer
This study has been terminated.
(due to a low response rate in a pre-planned efficacy evaluation)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00258349
First received: November 22, 2005
Last updated: January 3, 2013
Last verified: January 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Biological: trastuzumab Drug: vorinostat |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Response Rate [ 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 ] [ Designated as safety issue: No ]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.
Secondary Outcome Measures:
- Time to Progression [ 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 ] [ Designated as safety issue: No ]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.
- Overall Survival [ Time Frame: Survival was assessed every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry ] [ Designated as safety issue: No ]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.
| Enrollment: | 16 |
| Study Start Date: | August 2006 |
| Study Completion Date: | September 2010 |
| Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: vorinostat +trastuzumab |
Biological: trastuzumab
6 mg/kg once on Day 1, infused over 90 minutes, every 3 weeks
Other Names:
Drug: vorinostat
200 mg of Suberoylanilide Hydroxamic Acid (SAHA) orally twice a day, daily for 14 days out of a 21-day cycle
Other Names:
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00258349
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Show 45 Study LocationsSponsors and Collaborators
Investigators
| Study Chair: | Ramona Swaby, MD | Fox Chase Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00258349 History of Changes |
| Other Study ID Numbers: | NCI-2009-00503, U10CA021115, E1104, CDR0000449963 |
| Study First Received: | November 22, 2005 |
| Results First Received: | August 28, 2012 |
| Last Updated: | January 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Cancer Institute (NCI):
|
recurrent breast cancer stage IV breast cancer male breast cancer stage IIIB breast cancer stage IIIC breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Antibodies, Monoclonal Trastuzumab Vorinostat |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013