PARADIGM-2: olaparib radiotherapy temozolomide GBM
Research type
Research Study
Full title
PARADIGM-2: Olaparib and radiotherapy or olaparib and radiotherapy plus temozolomide in newly-diagnosed glioblastoma stratified by MGMT status: 2 parallel phase 1 studies.
IRAS ID
197457
Contact name
Anthony Chalmers
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Eudract number
2016-000865-22
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
PARADIGM-2 is a phase 1 study in patients with newly-diagnosed glioblastoma, which is the most aggressive type of primary brain tumour. Current treatments involve neurosurgery followed by radiotherapy which is often given in combination with oral chemotherapy tablets called temozolomide. The aim of PARADIGM-2 is to determine whether it is safe to add a new drug called olaparib to radiotherapy, with or without the oral chemotherapy tablets to establish the best dose of olaparib to be used in future clinical trials. This is called a phase 1study and investigates the safety of olaparib by escalating doses of the drug in combination with radiotherapy with or without chemotherapy in a pre-planned stepwise fashion. Patients will be allocated to one of two different treatment combinations depending on the genetic characteristics of their tumour. Glioblastoma tumours have areas of DNA called 'MGMT' which can be either 'methylated' or 'unmethylated.' Patients whose tumours have 'methylated' MGMT will receive olaparib in combination with radiotherapy and temozolomide (oral chemotherapy tablets). Patients whose tumours have
'unmethylated' MGMT will receive olaparib and radiotherapy, but not temozolomide. This is because tumours with 'unmethylated' MGMT are thought to be resistant to temozolomide. By avoiding temozolomide chemotherapy in this patient group we expect to be able to give higher doses of olaparib. The study will be conducted in 4 centres across the United Kingdom. Patients in the trial will be followed up within the trial until their tumour shows signs of regrowth.REC name
West of Scotland REC 1
REC reference
16/WS/0089
Date of REC Opinion
15 Jun 2016
REC opinion
Further Information Favourable Opinion