Randomized phase II study comparing the MET inhibitor cabozantinib to temozolomide (TMZ) or dacarbazine (DTIC) in ocular melanoma: A091201.

Background:  Ocular melanoma has been described to express the receptor tyrosine kinase MET in up to 80% of specimens and preclinical data suggests that MET inhibitors reduce proliferation and metastatic potential in cell lines and murine xenografts. Cabozantinib is a receptor tyrosine kinase inhibitor with significant inhibitory activity against MET and VEGFR2 (among other targets). Cabozantinib was associated with a median progression-free survival (mPFS) of 4.8 months in final follow up of the ocular melanoma cohort of the cabozantinib randomized discontinuation clinical trial. Notably, the MEK inhibitor selumetinib was determined to deliver mPFS of 3.9 months in a randomized phase II study.  Methods:  This is a national (Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group, NCIC Clinical Trials Group) open-label phase II study comparing cabozantinib with TMZ/DTIC in advanced ocular melanoma (clinicaltrials.gov: NCT01835145). The study randomizes patients 2:1 to cabozantinib and facilitates cross-over from the chemotherapy arm to cabozantinib at progression of disease. Eligibility is for any line of therapy and allows for prior treatment with MEK inhibitor or immunotherapy. Other eligibility includes biopsy proven metastatic ocular melanoma, ECOG 0-1 and adequate organ function (modified for elevated liver function tests related to hepatic metastases). The primary endpoint is PFS at 4 months with secondary endpoints evaluating RECIST response rate, PFS, overall survival and correlation of the primary endpoint with pre-treatment tumor tissue MET expression by IHC. The study is open to accrual via the Cancer Trials Support Unit (CTSU) of NCI to any cooperative group member site. Recruitment is on-going (target 69 patients). Clinical trial information: NCT01835145 or Alliance for Clinical Trials in Oncology # A091201.  Clinical trial information: NCT01835145.