Vorinostat in Treating Patients With Metastatic Melanoma of the Eye

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01587352
First received: April 26, 2012
Last updated: July 28, 2014
Last verified: June 2014

April 26, 2012
July 28, 2014
April 2012
June 2015   (final data collection date for primary outcome measure)
Overall response rate in patients with GNAQ/GNA11 mutant uveal melanoma, defined as the rate of complete and partial responses [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
The response rate along with 90% confidence interval will be estimated.
Overall response rate (complete and partial response) using a Simon mini-max two-stage design [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01587352 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: From start of treatment to death or last follow-up will be estimated, assessed up to 3 years ] [ Designated as safety issue: No ]
    Overall survival curves will be generated using Kaplan-Meier methodology.
  • Progression free survival [ Time Frame: From start of treatment to date of progression, death or last follow-up will be estimated, assessed up to 3 years ] [ Designated as safety issue: No ]
    Progression-free survival curves will be generated using Kaplan-Meier methodology.
  • Incidence of toxicities assessed by National Cancer Institute Common Toxicity Criteria 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Toxicity will be reported by type, frequency and severity.
  • Gnaq mutation status [ Time Frame: Up to day 15 ] [ Designated as safety issue: No ]
    Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
  • GNA11 mutation status [ Time Frame: Up to day 15 ] [ Designated as safety issue: No ]
    Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
  • BAP1 mutation status [ Time Frame: Up to day 15 ] [ Designated as safety issue: No ]
    Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
  • OS defined as the time from start treatment to death or last follow-up using Kaplan-Meier methodology [ Designated as safety issue: No ]
  • PFS defined as time from start of treatment to date of progression, death or last follow-up using Kaplan-Meier methodology [ Designated as safety issue: No ]
  • Toxicity reported by type, frequency and severity assessed by the National Cancer Institute Common Terminology Criteria version 4.0 [ Designated as safety issue: Yes ]
  • Association between GNAQ, GNA11, and BAP1 mutational status and overall response using Fisher's exact test [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vorinostat in Treating Patients With Metastatic Melanoma of the Eye
A Phase 2 Study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma

This phase II trial studies how well vorinostat works in treating patients with melanoma of the eye that has spread to other parts of the body. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the overall objective response rate (RR) to vorinostat in patients with metastatic uveal melanoma harboring a guanine nucleotide binding protein (G protein), q polypeptide (GNAQ) or guanine nucleotide binding protein (G protein), alpha 11 (Gq class) (GNA11 mutation).

SECONDARY OBJECTIVES:

I. Overall survival (OS). II. Progression free survival (PFS). III. To determine the tolerability of vorinostat in patients with metastatic uveal melanoma.

IV. To correlate overall objective RR with GNAQ, GNA11 and BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) (BAP1) mutational status.

TERTIARY OBJECTIVES:

I. To correlate clinical outcome with changes in histone acetylation status by immunohistochemistry.

II. To correlate clinical outcome with changes in known proliferation and apoptotic markers including Ki67 by immunohistochemistry and BCL2-like 11 (apoptosis facilitator) (BIM), baculoviral IAP repeat containing 5 (survivin), v-myc avian myelocytomatosis viral oncogene homolog (c-myc), myeloid cell leukemia 1 (Mcl-1), cleaved poly (ADP-ribose) polymerase 1 (PARP), gamma-H2A histone family, member X (gamma-H2AX) and RAD51 recombinase (RAD51) by western blot.

III. To assess for changes in pathways such as the mitogen-activated protein kinase (MAPK) pathway with treatment.

IV. To describe the evolution of circulating cell-free, tumor-derived deoxyribonucleic acid (DNA) levels measured by pyrophosphorolysis activated polymerization (PAP) in plasma of patients under treatment for metastatic uveal melanoma.

OUTLINE:

Patients receive vorinostat orally (PO) twice daily (BID) for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Metastatic Intraocular Melanoma
  • Recurrent Intraocular Melanoma
  • Drug: vorinostat
    Given PO
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (vorinostat)
Patients receive vorinostat PO BID for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: vorinostat
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
Not Provided
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT01587352
NCI-2012-00860, NCI-2012-00860, MSKCC-12-027, CDR0000732297, 12-027, 9111, N01CM62206, U01CA069856, P30CA008748
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Richard Carvajal Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP