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Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), July 2009
First Received: July 10, 2007   Last Updated: October 29, 2009   History of Changes
Sponsor: University of Pittsburgh
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00499811
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: vorinostat
Other: pharmacological study
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: Phase I and Pharmacokinetic Study of Vorinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pharmacokinetic variables corresponding to the disposition of vorinostat (SAHA) [ Designated as safety issue: No ]
  • Maximum tolerated dose and dose-limiting toxicity of vorinostat in groups of patients with varying degrees of hepatic dysfunction (mild, moderate, or severe) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity profile of vorinostat [ Designated as safety issue: Yes ]
  • Clinical response rate [ Designated as safety issue: No ]
  • Child-Pugh classification and liver function test results [ Designated as safety issue: No ]

Estimated Enrollment: 118
Study Start Date: June 2007
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the pharmacokinetic disposition of vorinostat (SAHA) in patients with metastatic or unresectable solid tumors or lymphoma and varying degrees of hepatic dysfunction.
  • 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).

Secondary

  • Document the non-DLTs associated with administration of vorinostat in patients with hepatic dysfunction.
  • Determine the association of the Child-Pugh classification of hepatic dysfunction with the observed toxicities, plasma pharmacokinetics, and pharmacodynamics of vorinostat administration.
  • 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).

  • 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 cycle of oral vorinostat will be initiated on a continuous daily oral regimen. Each treatment cycle 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • Life expectancy > 3 months
  • Absolute neutrophil count > 1,500/mm^3
  • Platelets ≥ 100,000/mm^3
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV-positive patients without an AIDS-defining diagnosis who are not receiving agents with the potential for pharmacokinetic interactions with vorinostat may be eligible
  • Able to take oral medications on a continuous basis
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No active hemolysis

PRIOR CONCURRENT THERAPY:

  • More than 3 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

    • Patients who have been treated with agents that persist in the body for longer than 4 to 6 weeks (such as suramin) are ineligible during the elimination period for those agents
  • More than 14 days since prior major surgery
  • No prior vorinostat
  • At least 2 weeks since prior valproic acid or other histone deacetylase inhibitors
  • More than 4 weeks since other prior investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent therapy with enzyme-inducing anticonvulsants
  • No concurrent prophylactic granulocyte growth factors during the first cycle of therapy
  • No other concurrent investigational or commercial agents or therapies
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00499811

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen     800-826-4673     becomingapatient@coh.org    
City of Hope Medical Group Recruiting
South Pasadena, California, United States, 91030
Contact: Mark V. McNamara, MD     626-396-2900     mmcnamara@ccsmg.com    
University of California Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Clinical Trials Office - University of California Davis Cancer     916-734-3089        
USC/Norris Comprehensive Cancer Center and Hospital Recruiting
Los Angeles, California, United States, 90089-9181
Contact: Clinical Trials Office - USC/Norris Comprehensive Cancer Cente     323-865-0451        
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Suresh Ramalingam, MD     404-778-1919        
United States, Maryland
NCI - Medical Oncology Branch Recruiting
Bethesda, Maryland, United States, 20892
Contact: Shivaani Kummar, MD     301-435-5402     kummars@mail.nih.gov    
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute     313-576-9363        
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Clinical Trials Office - Albert Einstein Cancer Center at Albe     718-904-2730     aecc@aecom.yu.edu    
United States, Ohio
Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Clinical Trials Office - Case Comprehensive Cancer Center     800-641-2422        
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Clinical Trials Office - Penn State Cancer Institute at Milton     717-531-3779     CTO@hmc.psu.edu    
UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers     412-647-8073        
United States, Texas
Institute for Drug Development Recruiting
San Antonio, Texas, United States, 78245-3217
Contact: Clinical Trials Office - Institute for Drug Development     800-340-2872        
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo     608-262-5223        
Sponsors and Collaborators
University of Pittsburgh
Investigators
Study Chair: Suresh Ramalingam, MD University of Pittsburgh
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000555102, PCI-07013, PCI-UPCI 07-013, NCI-07-C-0228
Study First Received: July 10, 2007
Last Updated: October 29, 2009
ClinicalTrials.gov Identifier: NCT00499811     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
recurrent adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
recurrent adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
cutaneous B-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage III grade 1 follicular lymphoma

Additional relevant MeSH terms:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Physiological Effects of Drugs
Ileal Diseases
Duodenal Neoplasms
Neoplasms by Site
Ileal Neoplasms
Sensory System Agents
Jejunal Diseases
Therapeutic Uses
Lymphoma, Large-Cell, Immunoblastic
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Digestive System Neoplasms
Immune System Diseases
Vorinostat
Enzyme Inhibitors
Intestinal Diseases
Protective Agents
Pharmacologic Actions
Intestinal Neoplasms
Lymphatic Diseases

ClinicalTrials.gov processed this record on February 08, 2010