Study of Tumor Samples in Patients Undergoing Radiation Therapy or Surgery For Primary Melanoma of the Eye

Prognostication of Uveal Melanoma by Fine Needle Aspiration (FNA) and Fluorescence in Situ Hybridization (FlSH)

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This clinical trial is studying tumor samples in patients undergoing surgery or radiation therapy for primary melanoma of the eye.

Study Overview

• Status: Completed
• Conditions: Intraocular Melanoma
• Intervention / Treatment: Genetic: fluorescence in situ hybridization; Other: laboratory biomarker analysis; Procedure: fine-needle aspiration; Procedure: therapeutic conventional surgery; Other: Questionnaires

Detailed Description

OBJECTIVES:

Primary

• To establish the feasibility of using fine needle aspiration (FNA) and FISH to determine tumor genotype in patients with primary uveal melanoma.

Secondary

• To characterize ophthalmic complication rate of FNA for FISH analysis in patients undergoing plaque radiotherapy.
• To estimate disease-free survival in patients with and without tumor monosomy 3 and/or 8q amplification.
• To explore the relationship between tumor monosomy 3 and 8q amplification and plasma levels of tumor immune escape and invasion biomarkers (e.g., circulating granulysin, beta2-microglobulin, autotoxin, lysophosphatidic acid, matrix metalloproteinase-7, tissue inhibitor of matrix metalloproteinase, and soluble E- cadherin).
• To explore the psychological impact of prognostication in uveal melanoma.

OUTLINE: Patients undergo plaque radiotherapy, enucleation, or tumor resection based upon standard of care guidelines.

Trans-scleral fine needle aspiration (FNA) is performed at the time of plaque radiotherapy and ex vivo FNA is performed on enucleation and tumor resection specimens. Tissue samples are analyzed by fluorescence in situ hybridization (FISH). Blood samples are also collected for further analysis.

After completion of study therapy, patients are followed up periodically.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Cole Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Primary Care Clinic

Description

Inclusion Criteria

• Patients must have a clinical diagnosis of melanoma of the iris, ciliary body and/or choroids
• Patients must have had a hepatic ultrasound and/or other suitable imaging studies to eliminate metastatic disease
• Patients must not have received any local or systemic therapy for uveal melanoma
• All patients must be informed of the investigational nature of this study and must provide written informed consent in accordance with institutional and federal guidelines. A copy of the informed consent document signed by the patient must be given to the patient

• Patients must have the following pretreatment laboratory findings:

  • Bilirubin (total) </= 1.5 ml/dl
  • AST </= 2 x normal
  • ALT </= 2 x normal
  • Alkaline phosphatase </= 2 x normal

Exclusion Criteria

• Patients with metastasis
• Patients under the age of 18

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients that have Disease Free Survival (DFS) with primary uveal melanoma with and without high-risk genotypes	DFS will be measured from the date of initial treatment to the date of documented recurrence or death. It will be summarized using the method of Kaplan and Meier.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events to determine ophthalmic complication rate of FNA for FISH analysis in patients undergoing plaque radiotherapy.	To characterize ophthalmic complication rate of FNA for FISH analysis in patients undergoing plaque radiotherapy.	2 years
The rate that sufficient tissue can be obtained by FNA.	Determine if sufficient material for FISH analysis can be obtained by transscleral FNA, a diagnostic procedure performed for a variety of clinical indications in patients with eye abnormalities.	2 yrs
distribution of particular markers at specific timepoints	Plasma will be analyzed for circulating granulysin, beta2-microglobulin, autotoxin, lysophosphatidic acid, matrix metalloproteinase-7, tissue inhibitor of matrix metalloproteinase, and soluble E-cadherin.	at baseline, multiple time points up to 2 years

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Arun D. Singh, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: August 5, 2009
• First Submitted That Met QC Criteria: August 5, 2009
• First Posted (Estimate): August 6, 2009

Study Record Updates

• Last Update Posted (Estimate): January 30, 2015
• Last Update Submitted That Met QC Criteria: January 28, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: ciliary body and choroid melanoma, medium/large size; iris melanoma; ciliary body and choroid melanoma, small size; intraocular melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: CASE5608 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); CASE 5608-CC666 (Other Identifier: Cancer Center IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No