PARADIGM-2: Two parallel phase I studies of olaparib and radiotherapy or olaparib and radiotherapy plus temozolomide in patients with newly diagnosed glioblastoma, with treatment stratified by MGMT status. (January 2018)

• Record Type: Journal Article
• Authors: Fulton, Ben; Short, Susan C.; James, Allan; Nowicki, Stefan; McBain, Catherine; Jefferies, Sarah; Kelly, Caroline; Stobo, Jon; Morris, Anna; Williamson, Aoife; Chalmers, Anthony J.
• Is Part Of: Clinical and translational radiation oncology. Volume 8(2018)
• Page Start: 12
• Page End: 16
• Publication Date: 2018-01
• Subjects: Glioblastoma -- Poly(ADP-ribose) polymerase -- Olaparib -- Radiotherapy -- O6-methylguanine methyltransferase -- Dose escalation -- Radiosensitizer; Cancer -- Radiotherapy -- Periodicals; Oncology -- Periodicals; Cancer -- Radiotherapy; Oncology; Radiation Oncology; Neoplasms -- radiotherapy; Translational Medical Research; Periodicals; Electronic journals; Periodicals; 616.9940642
• DOI: 10.1016/j.ctro.2017.11.003
• Languages: English
• ISSNs: 2405-6308

Abstract

Highlights: The manuscript details the rationale, design and protocol for PARADIGM-2. PARADIGM-2 comprises two parallel phase I, dose escalation studies of the PARP inhibitor olaparib in combination with radiotherapy (for MGMT unmethylated patients) and radiotherapy-temozolomide (for MGMT methylated patients) in newly diagnosed glioblastoma. This is a novel approach to phase I dose escalation trial design that maximises the potential for patients with glioblastoma to benefit from the addition of the radio- and chemosensitizing drug olaparib. Abstract: Glioblastoma has a dismal prognosis and molecular targeted agents have failed to improve outcomes to date. PARADIGM-2 is a phase I dose escalation study evaluating olaparib plus radiotherapy ± temozolomide in newly diagnosed glioblastoma, using MGMT methylation status to stratify patients and inform treatment schedules.