Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

NCT ID: NCT00499811

Last Updated: 2014-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

vorinostat

Intervention Type DRUG

Given orally

pharmacological study

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

vorinostat

Given orally

Intervention Type DRUG

pharmacological study

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

L-001079038 SAHA suberoylanilide hydroxamic acid Zolinza pharmacological studies

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Suresh Ramalingam

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope Medical Center

Duarte, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

National Institutes of Health

Bethesda, Maryland, United States

Site Status

Wayne State University-Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

West Virginia University Healthcare

Morgantown, West Virginia, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2009-00272

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-07-C-0228

Identifier Type: -

Identifier Source: secondary_id

CDR0000555102

Identifier Type: -

Identifier Source: secondary_id

PCI-UPCI 07-013

Identifier Type: -

Identifier Source: secondary_id

UPCI 07-013

Identifier Type: OTHER

Identifier Source: secondary_id

8057

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62208

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA099168

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062505

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062491

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062487

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA047904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00272

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.