Uveal MelanomaEarly Phase 1NCT03022565
Vorinostat in Patients With Class 2 High Risk Uveal Melanoma
A Early Phase 1 study testing Vorinostat in people with Uveal Melanoma, run by University of Miami.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- Vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2020to 29 Jan 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Uveal melanoma tumor determined by ophthalmic ultrasound or clinical assessment.
- Class 2 uveal melanoma
- No evidence of metastatic disease.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Life expectancy of greater than 3 months.
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- 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
- 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.
- 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.
- 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).
- Ability to understand the investigational nature, potential risks and benefits of the research study and to provide valid written informed consent.
Who cannot join
- Definitive therapy of the primary uveal melanoma by either surgery or radiotherapy
- 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.
- Any major surgery or extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to initiation of study therapy.
- History of prior vorinostat use.
- Use of other investigational drugs within 28 days
- 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).
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- 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.
- Concurrent administration of vorinostat and other HDAC inhibitors is not permitted due to the increased risk of thrombocytopenia and gastrointestinal bleeding.
- Patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with vorinostat.
- 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.
- History of pulmonary embolism (PT) or deep-vein thrombosis (DVT)
About this study
Official title: 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.
Read the 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.
- Conditions
- Uveal Melanoma
- Being tested
- Vorinostat
- Keywords
- Uveal Melanoma
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called Zolinza
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.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat | Experimental | Vorinostat:
* 400 mg orally, once daily for 15 days. Receives: Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of transformation from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
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).
Measured: 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.
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.
Measured: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Secondary outcomes (5)
Toxicity During Protocol Therapy
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.
Measured: Up to 1 Month Post-Treatment Completion
Tumor size before and after Vorinostat therapy
Tumor size will be determined before and after Vorinostat therapy by B-Scan ultrasonography.
Measured: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
Recurrence-free survival (RFS)
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.
Measured: Up to 5 Years Post-Treatment Completion
Overall survival (OS)
Overall Survival (OS) in Study Participants. OS is defined as the length of time from date of start of Vorinostat treatment to death.
Measured: Up to 5 Years Post-Treatment Completion
Disease Specific Survival (DSS)
Disease Specific Survival (DSS) in Study Participants. DSS is defined as the time from start of Vorinostat treatment to death due to disease.
Measured: Up to 5 Years Post-Treatment Completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study startJan 2020 (estimated)
- Primary completion29 Jan 2020
- Study completion29 Jan 2020
Why it stopped: Investigator Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- University of Miami Sylvester Comprehensive Cancer Center
- Responsible party
- Principal investigator, J. William Harbour, MD, University of Miami
- Investigators
- J. William Harbour, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03022565
- Sponsor's protocol ID
- 20160653
- Status last verified
- Feb 2020
- First submitted
- 21 Dec 2016
- Last updated
- 6 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Study of Vorinostat, A Histone Deacetylase Inhibitor, in Patients With Class 2 High Risk Uveal Melanoma
- ClinicalTrials.gov ID
- NCT03022565
- Acronym / sponsor ID
- 20160653
- Conditions
- Uveal Melanoma
- Keywords
- Uveal Melanoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator Decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- University of Miami Sylvester Comprehensive Cancer Center
- Study start
- Jan 2020 (estimated)
- Primary completion
- 29 Jan 2020 (actual)
- Study completion
- 29 Jan 2020 (actual)
- First posted
- 16 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat | Experimental | Drug: VorinostatVorinostat: * 400 mg orally, once daily for 15 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Uveal melanoma tumor determined by ophthalmic ultrasound or clinical assessment.
- Class 2 uveal melanoma
- No evidence of metastatic disease.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Key exclusion criteria (11 listed)
- Definitive therapy of the primary uveal melanoma by either surgery or radiotherapy
- 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.
- Any major surgery or extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to initiation of study therapy.
- History of prior vorinostat use.
- Use of other investigational drugs within 28 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatAlso: ZolinzaStudy 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. | Drug | Vorinostat |
Primary outcome
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).
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.
5 secondary outcomes
Toxicity During Protocol Therapy
Time frame: 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
Recurrence-free survival (RFS)
Time frame: Up to 5 Years Post-Treatment Completion
Overall survival (OS)
Time frame: Up to 5 Years Post-Treatment Completion
Disease Specific Survival (DSS)
Time frame: Up to 5 Years Post-Treatment Completion
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J. William Harbour, MD principal investigator
University of Miami
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vorinostat in people with Uveal Melanoma, run by University of Miami.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2020.