Vorinostat in Patients With Class 2 High Risk Uveal Melanoma

February 4, 2020 updated by: J. William Harbour, MD, University of Miami

Proof of Concept Study of Vorinostat, A Histone Deacetylase Inhibitor, in Patients With Class 2 High Risk Uveal Melanoma

This proof-of-concept study will evaluate the ability of vorinostat to induce the transformation of Class 2 uveal melanoma cells into a cell phenotype that resembles normal melanocytes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a proof of concept, single-center, open-label study of an FDA-approved drug, vorinostat, a Histone deacetylase (HDAC) inhibitor, for patients with Class 2, high-risk uveal melanoma with localized eye tumors. The primary aim is to test if vorinostat can transform aggressive class 2 uveal melanoma cells into cells that look more like normal melanocytes as observed in the laboratory. Uveal melanoma patients that meet the inclusion criteria outlined in this protocol will be consented and asked to provide a fine needle aspiration (FNA) biopsy of their uveal melanoma primary tumor. This biopsy will be submitted for gene expression analysis to determine the phenotype of the tumor. A total of 10 patients who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will be treated with 400 mg of vorinostat daily for 15 days. On Day 15, patients will be asked to provide a second FNA biopsy prior to receiving the standard of care local definitive therapy either plaque radiotherapy or enucleation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Uveal melanoma tumor determined by ophthalmic ultrasound or clinical assessment.
  2. Class 2 uveal melanoma
  3. No evidence of metastatic disease.
  4. Age ≥18 years.
  5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  6. Life expectancy of greater than 3 months.
  7. Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels

  8. Patients must have normal organ and marrow function as defined below:

    • Absolute neutrophil count (ANC) >1,500 cells/mm³
    • Platelet count >100,000/mm³
    • Hemoglobin >10.0g/dL
    • Aspartate transaminase (AST) and/or Alanine transaminase (ALT) < 3x upper limited of normal (ULN)
    • Total bilirubin < 2x ULN
    • Hemoglobin A1C ≤ 5.7%
    • Alkaline phosphatase < 3x ULN
    • Serum creatinine < 2x ULN or a creatinine clearance > 60 mL/min
    • Note: Patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator.
  9. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until 4 months after completion of study drug administration. Women of child-bearing potential must have a negative serum or urine test at time of enrollment. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study therapy, and 4 months after completion of study drug administration.
  10. Willingness to comply with all the visits and procedures (including providing all biological specimens) as required by the protocol and the informed consent form (ICF).
  11. Ability to understand the investigational nature, potential risks and benefits of the research study and to provide valid written informed consent.

Exclusion Criteria:

  1. Definitive therapy of the primary uveal melanoma by either surgery or radiotherapy
  2. History of another malignancy except for those who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy, are eligible. Consult the study Principal Investigator if unsure whether second malignancies meet the requirements specified above.
  3. Any major surgery or extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to initiation of study therapy.
  4. History of prior vorinostat use.
  5. Use of other investigational drugs within 28 days
  6. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to vorinostat (i.e. HDAC inhibitor hydroxamates such as panobinostat and belinostat).
  7. A QT interval corrected (QTc) for heart rate using the Bazett's formula (QTcB) ≥ 480 msec. Concurrent administration of vorinostat and agents that can cause QTc prolongation is not permitted.
  8. Concurrent administration of vorinostat and other HDAC inhibitors is not permitted due to the increased risk of thrombocytopenia and gastrointestinal bleeding.
  9. Patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with vorinostat.
  10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
  11. History of pulmonary embolism (PT) or deep-vein thrombosis (DVT)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vorinostat

Vorinostat:

  • 400 mg orally, once daily for 15 days.
Drug: Vorinostat
Study participants who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will be treated with 400 mg of Vorinostat daily for 15 days.
Other Names:
  • Zolinza

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Degree of transformation from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
Time Frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
The investigators will analyze gene expression results from fine needle aspirate biopsies performed at baseline prior to vorinostat therapy and post-treatment (on Day 15, after the planned 15 days of vorinostat therapy).
From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Proportion of patients whose tumors transformed from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
Time Frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Through gene expression analysis, the investigators will determine the proportion of patients whose tumors transformed from a Class 2 phenotype into a cell phenotype that resembles normal melanocytes.
From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Toxicity During Protocol Therapy
Time Frame: Up to 1 Month Post-Treatment Completion
Rate of adverse events (AEs) and serious adverse events (SAEs) experienced by study participants during Vorinostat therapy and up to one month after Vorinostat treatment completion.
Up to 1 Month Post-Treatment Completion
Tumor size before and after Vorinostat therapy
Time Frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Tumor size will be determined before and after Vorinostat therapy by B-Scan ultrasonography.
From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Recurrence-free survival (RFS)
Time Frame: Up to 5 Years Post-Treatment Completion
Recurrence-Free Survival (RFS) in Study Participants. RFS is defined as the duration of time from start of treatment to time of disease recurrence or death, whichever occurs first.
Up to 5 Years Post-Treatment Completion
Overall survival (OS)
Time Frame: Up to 5 Years Post-Treatment Completion
Overall Survival (OS) in Study Participants. OS is defined as the length of time from date of start of Vorinostat treatment to death.
Up to 5 Years Post-Treatment Completion
Disease Specific Survival (DSS)
Time Frame: Up to 5 Years Post-Treatment Completion
Disease Specific Survival (DSS) in Study Participants. DSS is defined as the time from start of Vorinostat treatment to death due to disease.
Up to 5 Years Post-Treatment Completion

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) before and after Vorinostat therapy.
Time Frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) will be measured at baseline (Day 1, before Vorinostat treatment) and post-treatment (day 15 after completion of Vorinostat therapy).
From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Miami

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Miami Sylvester Comprehensive Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: J. William Harbour, MD, University of Miami

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 29, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 29, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 21, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20160653

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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