Phase II Trial of SMO/ AKT/ NF2/CDK Inhibitors in Progressive Meningiomas with SMO/ AKT/ NF2/CDK Pathway Mutations

The purpose of this study is to test good and bad effects of these two different drugs against meningioma tumors with altered genes. Today, therapy for meningioma is the same for all patients, and is not based on tumor genetic testing. This trial is trying to see if tumor genetic testing would be helpful at guiding treatment in patients with meningioma. Researchers have looked at the DNA material (genes) that can be affected in meningioma and have found several genes that are altered, or mutated. These include the genes called SMO and NF2. When the SMO or NF2 genes are altered, it can cause a tumor to grow. There are medications that target these 2 genes. The medication, vismodegib, blocks the SMO receptor. Vismodegib has already been FDA-approved to treat basal cell cancer, which is a type of skin cancer. Vismodegib could shrink your meningioma, or your meningioma could stay the same size or grow. The medication, GSK2256098, blocks FAK, and seems to work better in tumors that have NF2-mutations. GSK2256098 has been tested in other cancers. GSK2256098 could shrink your meningioma, or your meningioma could stay the same size or grow. Researchers hope to learn if the study drugs will shrink the cancer by at least one-half compared to its present size.

Are you Eligible? (Inclusion Criteria)

• Tumor tissue must be available for submission to central laboratory
• Proven diagnosis of meningioma as determined by a central laboratory
• Presence of SMO or NF2 mutation in the tumor tissue as determined by a central laboratory
• Participant must be 18 years of age or older