Vorinostat in Patients With Class 2 High Risk Uveal Melanoma

NCT03022565 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 20160653
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Uveal Melanoma

Keywords

Uveal Melanoma

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks

Secondary Outcomes (5)

• Toxicity During Protocol Therapy

  Up to 1 Month Post-Treatment Completion

• Tumor size before and after Vorinostat therapy

  From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks

• Recurrence-free survival (RFS)

  Up to 5 Years Post-Treatment Completion

• Overall survival (OS)

  Up to 5 Years Post-Treatment Completion

• Disease Specific Survival (DSS)

  Up to 5 Years Post-Treatment Completion

Other Outcomes (1)

• Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) before and after Vorinostat therapy.

  From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks

Study Arms (1)

Vorinostat

EXPERIMENTAL

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

Drug: Vorinostat

Interventions

Vorinostat DRUG

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.

Also known as: Zolinza

Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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).
• 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)

Sponsors & Collaborators

• University of Miami: lead
• University of Miami Sylvester Comprehensive Cancer Center: collaborator

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• J. William Harbour, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: January 16, 2017
• Study Start: January 1, 2020
• Primary Completion: January 29, 2020
• Study Completion: January 29, 2020
• Last Updated: February 6, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share