Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction
|ClinicalTrials.gov Identifier: NCT00499811|
Recruitment Status : Completed
First Posted : July 11, 2007
Last Update Posted : February 24, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Primary Central Nervous System Hodgkin Lymphoma Primary Central Nervous System Non-Hodgkin Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Adult T-cell Leukemia/Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Mycosis Fungoides/Sezary Syndrome Stage III Small Lymphocytic Lymphoma Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Waldenström Macroglobulinemia||Drug: vorinostat Other: pharmacological study||Phase 1|
I. Determine the pharmacokinetic disposition of vorinostat (SAHA) in patients with metastatic or unresectable solid tumors or lymphoma and varying degrees of hepatic dysfunction.
II. Establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of vorinostat in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, or severe).
I. Document the non-DLTs associated with administration of vorinostat in patients with hepatic dysfunction.
II. Determine the association of the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma pharmacokinetics, and pharmacodynamics of vorinostat administration.
III. Document any antitumor activity associated with vorinostat treatment in patients enrolled on this study.
OUTLINE: This is a parallel-group, dose-escalation study. Patients are stratified according to level of hepatic dysfunction (normal vs mild vs moderate vs severe). (closed for accrual as of 04/05/2010)
PART I: Vorinostat (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.
PART II: 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.
Dose escalation will proceed within each hepatic dysfunction group (except in the normal group). Only dose-limiting toxicities (DLTs) that occur during the first cycle of treatment will be used to guide dose escalation. The maximum tolerated dose (MTD) is the highest dose at which no more than one instance of DLT is observed (among 6 patients treated). Once the MTD has been determined for a given hepatic dysfunction group, a maximum of 12 patients will be accrued to this dose level.
After completion of study treatment, patients are followed for 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I and Pharmacokinetic Study of Vorinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction|
|Study Start Date :||June 2007|
|Primary Completion Date :||August 2011|
Experimental: Treatment (enzyme inhibitor therapy)
Vorinostat (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.
Other Names:Other: pharmacological study
Other Name: pharmacological studies
- Pharmacokinetic (PK) variables corresponding to the disposition of vorinostat (SAHA) (Group 1) [ Time Frame: Days -6 and 1 of course 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.
- MTD of vorinostat based on incidence of DLT [ Time Frame: Up to 21 days ]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.
- Toxicity profile of vorinostat [ Time Frame: Up to 4 weeks after completion of treatment ]Toxicities will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category, grade. Tabulations will be separate for each liver dysfunction group, and may also be separate for each dose level within a group, if appropriate. For grade 3-4 toxicity, analyses will utilize Fisher's exact test.
- Clinical response rate [ Time Frame: Up to 4 weeks after completion of treatment ]Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
- Child-Pugh classification and liver function test results [ Time Frame: At baseline ]The Child-Pugh Classification and its association with toxicity and PK data will be studies in an exploratory analysis. For grade 3-4 toxicity, analyses will utilize Fisher's exact test; for PK data, the Wilcoxon test will be used. In addition, the correlation between the level(s) of liver dysfunction (bilirubin and/or synthetic (albumin), hepatocellular (bilirubin, ALT, AST) and/or ductal (gamma-GT, alkaline phosphatase) parameters and alterations in the PK of vorinostat will be evaluated with Spearman's test
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00499811
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|University of Southern California|
|Los Angeles, California, United States, 90033|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|National Institutes of Health|
|Bethesda, Maryland, United States, 20892|
|United States, Michigan|
|Wayne State University-Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467-2490|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, West Virginia|
|West Virginia University Healthcare|
|Morgantown, West Virginia, United States, 26506|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Suresh Ramalingam||University of Pittsburgh|