Bench to Bedside: From the Laboratory to the Pharmacy

OSU-14129 Adjuvant crizotinib’s effect on relapse-free survival in patients with uveal melanoma who are at high risk of recurrence following definitive therapy with surgery or radiotherapy

Hypothesis: That cMET inhibition with crizotinib will prevent the development of metastases in patients with high-risk primary uveal melanoma (UM, also called ocular melanoma). The addition of adjuvant crizotinib will increase relapse-free survival by 25 percent in UM patients at high risk of recurrence.

Study Design: This phase II, single-arm trial is designed to assess the 32-month rate of distant relapse in UM patients at high risk of recurrence following definitive therapy with surgery or radiation who receive adjuvant crizotinib. The study will also evaluate safety of the drug and determine overall survival and disease-specific survival.

Rationale: UM develops from melanocytes within the inner layers of the eye (choroid, ciliary body or iris). It represents about 5 percent of all melanomas and affects an estimated 2,000 people in the United States annually, mainly Caucasians. Approximately 85 percent of ocular melanomas are uveal in origin. No systemic therapy has been shown to improve survival in these patients, and about half of UM patients develop metastatic disease within 15 years of diagnosis. Median survival of distant metastatic disease is six to 12 months.

About 60-86 percent of UM cases overexpress c-MET, or the hepatocyte growth factor (HGF) receptor. Research has shown that crizotinib (already FDA approved for lung cancer) inhibits migration of UM cell lines through cMET inhibition.

This UM adjuvant trial was proposed based on the biological relevance of the HGF/cMET axis in UM, as it pertains to the preclinical data supporting the antimigratory and antitumor activity in this disease.

This is a multicenter trial in the United States. It is history-making in that is entirely funded by patient donations. Regardless of outcome, significant baseline data will be established for this tumor, giving physicians a good baseline for the development of future trials.

Thomas OlenckiAt a Glance

Trial no.: ClinicalTrial OSU-14129
gov identifier: NCT02223819

PI: Thomas Olencki, DO
Professor-clinical of Medical Oncology

Eligibility: All of the following: (1) Primary diagnosis of uveal melanoma with largest basal diameter greater than 12 mm, as clinically determined by the treating investigator; (2) Definitive therapy of the primary UM by surgery or radiotherapy within 120 days of initiating protocol therapy; (3) high-risk (Castle class 2) UM as determined by gene expression profiling; (4) no evidence of metastatic disease.

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