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Clinical Trial VICCMEL1351

Title

A Phase 2 study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma

Principal Investigator(s)

Jeffrey Sosman

Details

  • Protocol No. VICCMEL1351
  • Open Date: 10/17/2013
  • Staging: Phase II
  • Age Group: Adults
  • Scope: National
  • Objective: To determine the overall objective response rate (RR) to vorinostat in patients with metastatic uveal melanoma harboring a GNAQ or GNA11 mutation.
  • Disease Sites: Melanoma
  • Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
  • Drugs: Vorinostat (ZOLINZA)
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01587352
  • Secondary Protocol No: 12-027

Description

The purpose of this phase II clinical trial is to find out what effects; good and/or bad, vorinostat has on you and your uveal melanoma. Vorinostat is approved by the FDA for the treatment of certain lymphomas of the skin. Vorinostat treatment for uveal melanoma is experimental. Vorinostat is a medication that blocks a protein called histone deacetylase. In laboratory experiments, uveal melanoma cells stop growing and die after blocking histone deacetylase with vorinostat. We now want to see if vorinostat will result in tumor shrinkage in patients with uveal melanoma.

Eligibility

Ages Eligible for Study:18 Years and older
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No

Criteria

Inclusion Criteria:
• Patients must have metastatic histologically or cytologically confirmed uveal melanoma; (if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma); pathologic confirmation of diagnosis will be performed at Memorial Sloan-Kettering Cancer Center (MSKCC) or Vanderbilt University Medical Center
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9.0 g/dL not requiring transfusions within the past 2 weeks
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN); =< 3 x institutional ULN if the patient has Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN if no liver metastasis present; =< 5 x institutional ULN if liver metastases are present
• Creatinine =< 1.5 mg/dL
• Ability to understand and the willingness to sign a written informed consent document
• Tumor GANQ, GNA11, and BAP1 mutational status must be determined on all patients; if initial testing is performed locally or not available, MSKCC patients must consent to provide a tumor block or unstained slides to MSKCC for central review of mutational status; if tissue is not available, a pre-treatment biopsy will be necessary for eligibility
• Patients enrolled at Vanderbilt University Medical Center may have GNAQ and GNA11 mutational status determined on a Clinical Laboratory Improvement Act (CLIA)-approved assay at Vanderbilt University Medical Center or MSKCC; tissue must be sent to MSKCC for BAP1 mutational status determination
• The determination of mutational status may be performed retrospectively and will not delay patient treatment on study as long as tissue is available for molecular analysis
Exclusion Criteria:
• Patients may have had any number of prior therapies; at least 3 weeks must have elapsed since the last dose of systemic therapy; at least 6 weeks must have elapsed if the last regimen included BCNU or mitomycin C; at least 6 weeks must have elapsed if the last regimen included an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibody; patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator
• Patients who are receiving any other investigational agents
• Patients with active or untreated brain metastases; treated brain metastases must have been stable for at least 2 months
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
• Patients receiving histone deacetylase (HDAC) inhibitors or compounds with HDAC inhibitor like activity, such as valproic acid, are ineligible; patients who have received such agents may enroll on this study after a 14-day washout period
• Patients on warfarin will be excluded from the trial if they cannot be switched to an acceptable alternative medication (i.e. low molecular weight heparin [LMWH]); prolongation of prothrombin time (PT) and International Normalized Ratio (INR) were observed in patients receiving vorinostat concomitantly with coumarin-derivative anticoagulants
• Pregnant women are excluded from this study, breastfeeding should be discontinued if the mother is treated with vorinostat
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy will be eligible unless the cluster of differentiation (CD)4 count is < 200 cells/mm^3 within one month of study enrollment
• A second malignancy requiring active therapy
• No concomitant anti-cancer chemotherapy or other systemic drugs; palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Corrected QT interval (QTc) > 475 milliseconds
• Patients who cannot swallow capsules