INTERVENTIONALRECRUITING2021-005214-34

A Randomised Controlled Phase II Trial of Temozolomide With or Without Cannabinoids in Patients With Recurrent Glioblastoma

ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to compare the cannabinoid Nabiximols with placebo in patients with recurrent MGMT methylated glioblastoma (GBM) treated with temozolomide (TMZ).

Locally preserved from ISRCTN registryOpen ISRCTN registrylast source update 2026-05-05

What this record can show

Registry results are available

Registry submitter results are candidate evidence, not independent verification.

Registry facts

Study at a glance

Phase: PHASE2
Enrollment: 120 (ESTIMATED)
Start date: 2023-02-03
Sponsor: University of Birmingham
Design: Not reported
Locations: 5
Results record: Present in registry snapshot

This is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to compare the cannabinoid Nabiximols (Sativex®) with placebo in patients with recurrent MGMT methylated glioblastoma treated with temozolomide (TMZ). The trial will randomise a target number of 120 patients on a 2:1 basis to receive either Nabiximols or Nabiximols-matched placebo, in combination with standard TMZ. Patients will be followed up at 4-weekly assessments for a minimum of 52 weeks from the start of trial treatment or until death, whichever is sooner. MRI scanning will be performed at screening, week 10, week 22, week 30, then 3-monthly after commencing trial treatment as per standard practice. The trial includes an initial feasibility study of 40 patients to confirm safety, compliance and achievability of planned target recruitment. There are no formal criteria for evaluation of feasibility but once 40 patients have been recruited, the independent Data Monitoring Committee will review the adverse event data, details on protocol treatment received, monthly recruitment rates and projected recruitment in order to make recommendations on trial continuation. The original phase II trial design allowed potential expansion of recruitment into a phase III trial, should the emerging phase II results warrant this development; however, the trial was revised to a standard phase II design to lower the recruitment targets in 2025 The trial will be linked to the Tessa Jowell BRAIN MATRIX (TJBM) programme; utilising TJBM infrastructure, opening the same participating sites, and aligning the data collection and Quality of Life assessments already embedded in TJBM. This collaboration will allow data sharing within the platform thereby streamlining patient entry and provide additional oversight through TJBM. Patients recruited to TJBM who are potentially eligible for ARISTOCRAT may be identified and suggested to sites for consideration to the trial.

Linked local records

Related local records

Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.

Conditions

No published condition report matched.

Cannabinoids and active compounds

No governed compound link was found.

Medicines

SATIVEX

Interventions

What was registered

Drug

Sativex (cannabinoids), temozolomide

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 each 28-day cycle, up to a maximum of 6 cycles. In addition to standard TMZ, patients will receive Sativex or Sativex-matched placebo, up to 12 sprays per day up to a maximum of 6 cycles, self-titrated over days 1-14 in cycle 1. Patients will be randomised to trial medication in a double-blinded manner using a computer minimisation technique developed by CRCTU.

Sativex (cannabinoids), temozolomide

Source-reported results

Results posted to the registry

0 outcomes

Registry submitter results are candidate evidence, not independent verification.

Primary outcomes: 0
Secondary outcomes: 0
Statistical analyses: 0
Adverse-event terms: 0

Eligibility

Population and criteria

Sex: All
Minimum age: 16 Years
Maximum age: 100 Years
Healthy volunteers: Not reported

Eligibility 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 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

primary outcomes

primary measures

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 outcomes

secondary measures

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

Publications

Locally readable linked articles

background reference

A randomised phase II trial of temozolomide with or without cannabinoids in patients with recurrent glioblastoma (ARISTOCRAT): protocol for a multi-centre, double-blind, placebo-controlled trial.

BMC Cancer · Free full text

Snapshot provenance

Snapshot: 9d5a765d-a1f3-492f-895e-e93468091fd4
Retrieved: 24/09/2026, 15:03:38
SHA-256: 05ea461e4a9cd0e8c9d73e18b0c48902e8a32c2104041648c5a2396bec2416aa

A Randomised Controlled Phase II Trial of Temozolomide With or Without Cannabinoids in Patients With Recurrent Glioblastoma

Registry results are available

Study at a glance

Related local records

Conditions

Cannabinoids and active compounds

Medicines

What was registered

Sativex (cannabinoids), temozolomide

Results posted to the registry

Population and criteria

Eligibility criteria

Inclusion criteria

Inclusion criteria

primary measures

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 measures

Locally readable linked articles

A randomised phase II trial of temozolomide with or without cannabinoids in patients with recurrent glioblastoma (ARISTOCRAT): protocol for a multi-centre, double-blind, placebo-controlled trial.

Inclusion criteria

Exclusion criteria

Exclusion criteria

Exclusion criteria