Phase II Study of Olaparib in Metastatic Renal Cell Carcinoma Patients Harboring a BAP-1 or Other DNA Repair Gene Mutations (ORCHID).
Johns Hopkins Kimmel Cancer Center in Baltimore
The purpose of the study is to evaluate efficacy based on objective response or stable disease at 6 months to Olaparib in patients with BAP-1 or other DNA repair gene mutated renal cell carcinoma.
Patients must meet all eligibility criteria to be enrolled in the study. Eligible patients are those with metastatic renal cell carcinoma (either clear cell or non-clear cell) after progression on AT LEAST one VEGF-targeted therapy or immune checkpoint inhibitor. There is no limit to prior therapies.All patients must have a documented germline or somatic mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment. No prior treatment with PARP inhibitor including Olaparib is allowed.
This is an open-label single-arm phase II trial. The patients will be treated with Olaparib at an initial dose of 150mg by mouth twice daily, since many patients with metastatic renal cell carcinoma have had a prior nephrectomy and underlying renal insufficiency. If Olaparib is tolerated without any significant adverse events after 1 month, the dose will be increased to the FDA approved dose of 300mg by mouth twice daily. Patients will be followed monthly with clinic visits, safety labs, and toxicity assessments. Treatment will be continued until radiographic progression or unmanageable toxicity requiring drug cessation.
08/08/2020 05:02 AM