Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction
Phase I and Pharmacokinetic Study of Vorinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction
12 other identifiers
interventional
15
1 country
11
Brief Summary
This phase I trial is studying the side effects and best dose of vorinostat in treating patients with metastatic or unresectable solid tumors or lymphoma and liver dysfunction. (closed for accrual as of 04/05/2010) Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Vorinostat may have different effects in patients who have changes in their liver function.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2007
CompletedFirst Submitted
Initial submission to the registry
July 10, 2007
CompletedFirst Posted
Study publicly available on registry
July 11, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2011
CompletedFebruary 24, 2014
October 1, 2011
4.2 years
July 10, 2007
February 21, 2014
Conditions
Outcome Measures
Primary Outcomes (2)
Pharmacokinetic (PK) variables corresponding to the disposition of vorinostat (SAHA) (Group 1)
The Wilcoxon test will be used for PK data. Concentrations of vorinostat and 2 metabolites (vorinostat glucuronide and 4-anilino-4-oxobutanoic acid) will be quantitated with a liquid chromatography-electrospray ionization tandem mass spectrometric method that was developed and validated in our laboratory. Plasma concentration versus time data for vorinostat and metabolites will be analyzed non-compartmentally using the LaGrange function as implemented by the Lagran computer program.
Days -6 and 1 of course 1
MTD of vorinostat based on incidence of DLT
The MTD is the highest dose at which no more than one instance of DLT is observed (among 6 patients treated). The MTDs determined in this study represent a simple summary of the relationship between the dose of vorinostat that can be administered with acceptable toxicity and a patient's level of liver dysfunction. Treatment-related events occurring during the first course of treatment are considered DLTs.
Up to 21 days
Secondary Outcomes (3)
Toxicity profile of vorinostat
Up to 4 weeks after completion of treatment
Clinical response rate
Up to 4 weeks after completion of treatment
Child-Pugh classification and liver function test results
At baseline
Study Arms (1)
Treatment (enzyme inhibitor therapy)
EXPERIMENTALVorinostat (SAHA) will be administered as a single oral dose on day -6 for all patients. Blood samples are obtained periodically on day -6 for pharmacokinetic studies. One week later (day 1), the first course of oral vorinostat will be initiated on a continuous daily oral regimen. Each treatment course will consist of 21 days of therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions
Given orally
Correlative studies
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable
- Patients with a liver mass, elevated α-fetoprotein level (≥ 500 ng/mL), and positive serology for hepatitis consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis
- Standard curative or palliative measures do not exist or are no longer effective
- Patients who have not received any prior therapy for malignancy are also eligible if they are ineligible for standard therapy due to hepatic dysfunction
- Patients with abnormal liver function will be eligible
- No distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes
- Patients with biliary obstruction for which a shunt has been placed are eligible, provided the shunt has been in place for at least 10 days prior to the first dose of vorinostat (SAHA) and liver function has stabilized
- Two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function
- No evidence of biliary sepsis
- Patients with gliomas or brain metastases who require corticosteroids or anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to study enrollment
- Patients with known brain metastases should have had brain irradiation (whole brain or gamma knife) more than 4 weeks before starting protocol treatment
- Patients with unstable or untreated (non-irradiated) brain metastases should be excluded
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
- Life expectancy \> 3 months
- Absolute neutrophil count \> 1,500/mm\^3
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
City of Hope Medical Center
Duarte, California, 91010, United States
University of Southern California
Los Angeles, California, 90033, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
National Institutes of Health
Bethesda, Maryland, 20892, United States
Wayne State University-Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Montefiore Medical Center
The Bronx, New York, 10467-2490, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Suresh Ramalingam
University of Pittsburgh
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 10, 2007
First Posted
July 11, 2007
Study Start
June 1, 2007
Primary Completion
August 1, 2011
Last Updated
February 24, 2014
Record last verified: 2011-10