Glioblastoma Cancer
Conditions
Interventions
Parallel 1 (Methylation of MGMT promoter region) – Patients will receive partial brain radiotherapy, consisting of 60 Gray in 30 fractions over 6 weeks (Monday to Friday), planned and delivered using
Sponsors
NHS Greater Glasgow & Clyde and University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 100g/L (no red blood cell transfusions in the 28 days prior to trial entry) 8.2. Absolute neutrophil count >1.5 x 109/L 8.3. White Blood Cells >3 x 109/L 8.4. Platelet count > 100 x 109/L 8.5. Bilirubin 50 ml/min calculated by Cockcroft-Gault/Wright formula 9. Able to commence radiotherapy treatment within 6 weeks (+ 1 week if necessary) of surgery 10. Willingness to comply with scheduled visits, treatment plans, laboratory tests and any other trial procedures 11. Ability to swallow oral tablets or capsules 12. Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days of trial entry Postmenopausal is defined as: 12.1. Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments 12.2. LH and FSH levels within the postmenopausal range for women under 50 12.3. Surgical sterilisation (bilateral oophrectomy or hysterectomy)
Exclusion criteria
Exclusion criteria: 1. Age =70 years 2. WHO performance status >2 3. Life expectancy less than 12 weeks 4. Active concurrent malignancy (except non-melanoma skin cancer or in-situ carcinoma of the cervix). If history of prior malignancy, must be disease-free for >5 years 5. Prior treatment for primary or secondary CNS malignancies 6. Confusion or altered mental state that would prohibit patient understanding and giving of informed consent 7. Concomitant treatment with medicines detailed in section 5.8 of the PARADIGM-2 protocol 8. Female patients who are able to become pregnant (or are already pregnant or lactating). Lactating patients should not breastfeed during treatment or for 1 month after the last dose of olaparib. However, those female patients who have a negative serum or urine pregnancy test before enrolment and are not lactating and agree to the use of two highly effective forms of contraception (as detailed in section 7.1.7) effective at the first administration of IMP, throughout the trial and for at least one month afterwards are considered eligible 9. Male partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception, as detailed in section 7.1.7, effective at the time of administration of IMP, throughout the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate 10. Administration of any investigational drug within 28 days prior to receiving the first dose of trial treatment 11. Any previous treatment with a PARP inhibitor, including olaparib 12. Any red blood cell transfusions within 28 days prior to trial entry (platelet and clotting factor transfusions are allowed) 13. Patients with myelodysplastic syndrome/acute myeloid leukaemia 14. Major surgery within 14 days of starting trial treatment; patients must have recovered from any effects of major surgery 15. Patients with a known hypersensitivity to any of the excipients of olaparib, temozolomide or dacarbazine (DTIC) 16. Patients with uncontrolled seizures 17. Patients who are known to be HIV positive, or who are known to have positive Hepatitis B or C serology
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The maximum tolerated dose and schedule of olaparib in combination with radiotherapy and temozolomide (parallel 1) and in combination with radiotherapy alone (parallel 2). This will be measured by clinical and laboratory toxicity, NCI-CTC version 4.03. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Toxicity, including acute and subacute neurotoxicity – measured by clinical and laboratory toxicity, NCI-CTC version 4.03 2. Progression free survival – measured by MRI scan, reported using RANO criteria 3. Overall survival – measured by date of death/date patient last assessed | — |
Countries
England, Scotland, United Kingdom, Wales
Outcome results
None listed