Glioblastoma multiforme Cancer
Conditions
Interventions
All patients in Arm 1 and Arm 2 will receive standard temozolomide (TMZ). This is 150mg/m2 for cycle 1, increasing to 200mg/m2 for subsequent cycles, once daily for days 1-5 orally at the start of eac
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
16 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 06/06/2025: 1. Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) glioblastoma multiforme (GBM) with consistent local molecular pathology (repeat biopsy at recurrence is NOT required) 2. First recurrence of GBM planned for systemic treatment as determined by local Multidisciplinary Team (MDT), including agreement of a Consultant Neuro-Radiologist that imaging changes are most in keeping with recurrence and not pseudo-progression and patient is planned for systemic treatment. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment. 3. Patients must have received initial first-line treatment with standard dose conventionally fractionated radiotherapy (i.e., 40 Gy in 15 fractions or 54-60 Gy in 28-33 fractions; other regimes may be considered in consultation with the ARISTOCRAT Trial Office) with concomitant and adjuvant temozolomide (TMZ) 3.1 Minimum of 3 cycles of adjuvant TMZ must have been received 3.2. Minimum of Stable Disease (SD) (or Partial Response (PR)/Complete Response (CR)) at the end of first-line treatment 4. =3 months since day 28 of the last cycle of TMZ 5. Karnofsky Performance Status =60 6. Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation: 6.1. Absolute neutrophil count (ANC) =1.5 x 109/L 6.2. Platelet count =100 x 109/L 6.3. Serum creatinine clearance (measured or calculated (using local standard practice)) >30 ml/min 6.4. Total serum bilirubin =1.5 x upper limit of normal (ULN) 6.5. Liver transaminases <2.5 x ULN 7. If surgery has been performed for first recurrence then the wound must be adequately healed and there must be residual enhancing disease on MRI within 21 days of surgery or new enhancement at later follow-up deemed suitable for systemic treatment 8. Recovered from previous treatment side-effects = Grade 2 9. If on systemic steroids, must be on stable (=7 days) or decreasing dose of steroids 10. Willing and able to provide trial-specific informed consent 11. Willing and able to comply with trial requirements 12. Aged 16 years old and over 13. Able to start treatment within 28 days of randomisation Previous inclusion criteria as of 31/08/2023: 1. Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) glioblastoma multiforme (GBM) with consistent local molecular pathology (repeat biopsy at recurrence is NOT required) 2. First recurrence of GBM planned for systemic treatment as determined by local Multidisciplinary Team (MDT), including agreement of a Consultant Neuro-Radiologist that imaging changes are most in keeping with recurrence and not pseudo-progression and patient is planned for systemic treatment. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment. 3. Patients must have received initial first-line treatment with standard dose conventionally fractionated radiotherapy (i.e., 40 Gy in 15 fractions or 54-60 Gy in 28-33 fractions; other regimes may be considered in consultation with the ARISTOCRAT Trial Office) with concomitant and adjuvant temozolomide (TMZ) 3.1 Minimum of 3 cycles of adjuvant TMZ must have been received 3.2. Minimum of SD (or PR/CR) at the end of first-line treatment 4. =3 months since day 28 of the last cycle of TMZ 5. Karnofsky Performance Status =60 6. Adequate hematologic, renal, and hepatic function wit
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 06/06/2025: 1. Pathology inconsistent with IDH WT glioblastoma multiforme (GBM) (e.g. patients with molecular features of PXA or BRAF mutation will be excluded) 2. Prior invasive malignancy (except non-melanoma skin cancer), unless disease free for a minimum of one year 3. Prior treatment with stereotactic radiotherapy, brachytherapy or Convection Enhanced Delivery (CED) of any agent 4. Prior treatment, apart from debulking surgery, for first recurrence of GBM 5. Any active co-morbidity making patient unsuitable for trial treatment in the view of the Investigator 6. Personal history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric diagnosis other than depression associated with their underlying glioma condition 7. Prior allergic reaction or significant toxicity (=Grade 3 CTCAE) related to temozolomide treatment 8. Current or recent cannabis or cannabinoid-based medications within 28 days of randomisation and/or unwilling to abstain for the duration of the trial 9. Women who are pregnant, breastfeeding or a woman of childbearing potential who is unwilling to use effective contraceptive methods during trial treatment and for 6 months after completion of trial treatment 9.1. Women of childbearing age must have a negative pregnancy test within 7 days prior to randomisation 10. Men who are sexually active and unwilling/unable to use medically acceptable forms of contraception during trial treatment or for 6 months after completion of trial treatment 11. Contraindication to MRI or gadolinium 12. Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 13. Known hypersensitivity to cannabinoids or excipients of the IMP 14. Known history of current or prior alcohol or drug dependence 15. Known Hepatitis B (HBV), Cytomegalovirus (CMV) or opportunistic infection 16. Has received a live vaccine within 28 days prior to randomisation 17. Unable to administer oromucosal medication due to mucosal lesions or other issues 18. Participation in another therapeutic clinical trial whilst taking part in this trial 19. Any psychological, familial, sociological or geographical condition hampering protocol compliance Previous exclusion criteria as of 08/11/2022: 1. Pathology inconsistent with IDH WT glioblastoma multiforme (GBM) (e.g. patients with molecular features of PXA or BRAF mutation (on original pathology) will be excluded) 2. Prior invasive malignancy (except non-melanoma skin cancer), unless disease free for a minimum of one year 3. Prior treatment with stereotactic radiotherapy, brachytherapy or Convection Enhanced Delivery (CED) of any agent 4. Prior treatment, apart from debulking surgery, for first recurrence of GBM 5. Any active co-morbidity making patient unsuitable for trial treatment in the view of the Investigator 6. Personal history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric diagnosis other than depression associated with their underlying glioma condition 7. Prior allergic reaction or significant toxicity (=Grade 3 CTCAE) related to temozolomide treatment 8. Current or recent cannabis or cannabinoid-based medications within 30 days of randomisation and/or unwilling to abstain for the duration of the trial 9. Women who are pregnant, breastfeeding or a woman of childbearing potential who is unwilling to use effective contraceptive methods during trial treatme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival time (OS), defined as the time in whole days from the date of randomisation to the date of death from any cause, measured using patient survival until the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival measured using patient survival at 12 months (and 6 and 24 months) 2. Progression-free survival time, defined as the time in whole days from the date of randomisation to the date of the first documented evidence of disease progression or death (from any cause), measured using Response Assessment for Neuro-Oncology (RANO) criteria at screening, weeks 10, 22, 30 then 3 monthly (as per standard of care) for up to a minimum of 52 weeks from the start of trial treatment 3. Health-related quality of life measured using the EORTC QLQ-C30, EORTC BN20, single items from the EORTC item library, and the EQ-5D-5L at screening and then every 8 weeks until the end of treatment 4. Adverse events measured using CTCAE v5.0 at 4-weekly intervals post-start of treatment up to progression or withdrawal | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactRhys Mant
Outcome results
None listed