Vorinostat in Patients With Class 2 High Risk Uveal Melanoma

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Brief Title

Vorinostat in Patients With Class 2 High Risk Uveal Melanoma

Official Title

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

Brief 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.
    

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 Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Degree of transformation from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.

Secondary Outcome

 Toxicity During Protocol Therapy

Condition

Uveal Melanoma

Intervention

Vorinostat

Study Arms / Comparison Groups

 Vorinostat
Description:  Vorinostat:
400 mg orally, once daily for 15 days.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

January 2020

Completion Date

January 29, 2020

Primary Completion Date

January 29, 2020

Eligibility Criteria

        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)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

J. William Harbour, MD, , 



Administrative Informations


NCT ID

NCT03022565

Organization ID

20160653


Responsible Party

Principal Investigator

Study Sponsor

University of Miami

Collaborators

 University of Miami Sylvester Comprehensive Cancer Center

Study Sponsor

J. William Harbour, MD, Principal Investigator, University of Miami


Verification Date

February 2020