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Vorinostat in Treating Patients With Metastatic Melanoma of the Eye

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01587352
Recruitment Status : Suspended (Other - Non-compliance with sponsor data reporting requirements)
First Posted : April 30, 2012
Last Update Posted : May 21, 2020
Sponsor:
Collaborators:
Institut Curie Paris
Memorial Sloan Kettering Cancer Center
Moffitt Cancer Center P2C
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE April 26, 2012
First Posted Date  ICMJE April 30, 2012
Last Update Posted Date May 21, 2020
Actual Study Start Date  ICMJE April 20, 2012
Estimated Primary Completion Date November 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2014)
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 ]
The response rate along with 90% confidence interval will be estimated.
Original Primary Outcome Measures  ICMJE
 (submitted: April 26, 2012)
Overall response rate (complete and partial response) using a Simon mini-max two-stage design
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
  • Overall survival [ Time Frame: From start of treatment to death or last follow-up will be estimated, assessed up to 3 years ]
    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 ]
    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 ]
    Toxicity will be reported by type, frequency and severity.
  • Gnaq mutation status [ Time Frame: Up to day 15 ]
    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 ]
    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 ]
    Associations of each unique mutation status with overall response will be assessed using Fisher's exact test.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2012)
  • OS defined as the time from start treatment to death or last follow-up using Kaplan-Meier methodology
  • PFS defined as time from start of treatment to date of progression, death or last follow-up using Kaplan-Meier methodology
  • Toxicity reported by type, frequency and severity assessed by the National Cancer Institute Common Terminology Criteria version 4.0
  • Association between GNAQ, GNA11, and BAP1 mutational status and overall response using Fisher's exact test
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vorinostat in Treating Patients With Metastatic Melanoma of the Eye
Official Title  ICMJE A Phase 2 Study of Vorinostat (NSC 701852) in Metastatic Uveal Melanoma
Brief Summary 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.
Detailed Description

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 breast cancer 1 (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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ocular Melanoma With Extraocular Extension
  • Recurrent Uveal Melanoma
  • Stage IV Uveal Melanoma AJCC v7
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Vorinostat
    Given PO
    Other Names:
    • L-001079038
    • MSK-390
    • SAHA
    • Suberanilohydroxamic Acid
    • Suberoylanilide Hydroxamic Acid
    • Zolinza
Study Arms  ICMJE 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:
  • Other: Laboratory Biomarker Analysis
  • Drug: Vorinostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: September 26, 2019)
40
Original Estimated Enrollment  ICMJE
 (submitted: April 26, 2012)
32
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date November 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Columbia University, 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
  • Women of child-bearing potential and men must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of vorinostat administration
  • Tumor GANQ, GNA11, and BAP1 mutational status must be determined on all patients; if initial testing is performed locally or not available, MSKCC or Columbia University Medical Center (CUMC) patients must consent to provide a tumor block or unstained slides to MSKCC or CUMC 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, CUMC, 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01587352
Other Study ID Numbers  ICMJE NCI-2012-00860
NCI-2012-00860 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CUMC-IRBAAAO5917
AAAO5917
MSKCC-12-027
AAAO5917 ( Other Identifier: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center )
9111 ( Other Identifier: CTEP )
N01CM00100 ( U.S. NIH Grant/Contract )
N01CM62206 ( U.S. NIH Grant/Contract )
P30CA013696 ( U.S. NIH Grant/Contract )
U01CA069856 ( U.S. NIH Grant/Contract )
UM1CA186689 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE
  • Institut Curie Paris
  • Memorial Sloan Kettering Cancer Center
  • Moffitt Cancer Center P2C
Investigators  ICMJE
Principal Investigator: Richard D Carvajal Columbia University/Herbert Irving Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date March 2020

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