This is a phase II multi-center prospective basket trial designed to test the hypothesis that targeting specific kinase fusions in metastatic melanoma with pre-specified kinase inhibitors will result in objective tumor shrinkage and durable response. The study design is a 2 stage optimal design with a sample size of N=35, with n1=11 during stage I and n2=24 during stage II. If 1 or fewer responses are observed during stage I, the trial will be stopped. If 6 or fewer responses are observed by the end of stage II, the trial will be stopped.
Phase II Trial Of Targeted Kinase Fusion Inhibition in Unresectable Stage III/IV BRAF/NRAS Wild-Type Melanoma
This is a phase II prospective multi-center basket trial designed to test the hypothesis that targeting specific kinase fusions in metastatic melanoma with kinase inhibitors matched to the activated kinase fusion will result in tumor response. The study design is a 2-stage optimal design. Patients will be screened for one of the eligible fusion proteins using various assays developed in a CLIA-approved laboratory (targeted next-generation sequencing of tumor tissue, fluorescence in situ hybridization and immunohistochemistry) under a separate protocol. If identified, patients will be offered enrollment in this protocol and will be treated in one of five baskets.
The dose of INC280 at 600 mg PO BID is based on the recommended phase II dose (RP2D) by Novartis. The dose of ceritinib at 750 mg PO daily is the FDA-approved dose for ALK-rearranged NSCLC resistant to intolerant to crizotinib. For regorafenib we will dose at 160 mg PO daily (first 21 days of each 28 day cycle) which is the FDA-approved dose for both colon cancer and GIST. The dose of entrectinib at 600 mg PO QD is the RP2D based on two Phase 1 studies conducted by Ignyta.
Melanoma Metastatic BRAF Wild-Type (WT) NRAS Wild-Type (WT) KRAS Wild-Type (WT) HRAS Wild-Type (WT) GNAQ Wild-Type (WT) GNA11 Wild-Type (WT) KIT Wild-Type (WT) Ceritinib
For people ages 18 years and up
General: Inclusion Criteria
General: Exclusion Criteria
Uncontrolled hypertension (systolic pressure ≥160 mmHg or diastolic pressure
≥100 mmHg on repeated measurement) despite optimal medical management. Initiation or adjustment of antihypertensive medications are allowed prior to screening.
Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug- lists.cfm)
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