Home › Trials › NCT05629702

Comparing Nabiximols with placebo for treating recurrent glioblastoma with temozolomide

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

Phase 2 Interventional University of Birmingham · NCT05629702

This study is testing if a cannabis-based treatment called Nabiximols can help people with recurring glioblastoma when used alongside a standard drug called temozolomide.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment120 (estimated)
Ages16 Years and up
SexAll
SponsorUniversity of Birmingham Academic / other
Locations22 sites (Bodelwyddan, Denbighshire and 21 other locations)
Trial IDNCT05629702 on ClinicalTrials.gov

What this trial studies

ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled trial designed to evaluate the efficacy of the cannabinoid Nabiximols in combination with temozolomide for patients with recurrent MGMT methylated glioblastoma. The study will randomize 234 patients to receive either Nabiximols or a matched placebo, with follow-up assessments every four weeks for at least 52 weeks. MRI scans will be conducted at specified intervals to monitor treatment response. An initial feasibility study involving 40 patients will assess safety and recruitment before proceeding with the full trial.

Who should consider this trial

Good fit: Ideal candidates are patients with recurrent MGMT methylated glioblastoma who have previously received standard treatment with temozolomide and radiotherapy.

Not a fit: Patients with glioblastoma that is not MGMT methylated or those who have not undergone prior treatment with temozolomide may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a new therapeutic option that enhances the effectiveness of temozolomide in treating recurrent glioblastoma.

How similar studies have performed: While the use of cannabinoids in cancer treatment is being explored, this specific combination approach is novel and has not been extensively tested in prior studies.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histological diagnosis of MGMT promoter methylated, IDH wild type (WT) GBM with consistent local molecular pathology (repeat biopsy at recurrence is NOT required).
* 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. Patients with a prior recurrence treated by surgical resection alone are eligible at time of first recurrence planned for systemic treatment.
* 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 TMZ.

  * A minimum of 3 cycles of adjuvant TMZ must have been received.
  * A minimum of Stable Disease (SD) (or Partial Response (PR)/Complete Response (CR)) at the end of first-line treatment (measured by Response Assessment for Neuro-Oncology (RANO) criteria).
* ≥3 months since day 28 of the last cycle of TMZ.
* Karnofsky Performance Status ≥60.
* Adequate hematologic, renal, and hepatic function within 14 days prior to randomisation:

  * Absolute neutrophil count (ANC) ≥1.5 x 109/L
  * Platelet count ≥100 x 109/L
  * Serum creatinine clearance (measured or calculated (using local standard practice)) \>30ml/min
  * Total serum bilirubin ≤1.5 x upper limit of normal (ULN)
  * Liver transaminases \<2.5 x ULN
* 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.
* Recovered from previous treatment side-effects ≤ Grade 2.
* If on systemic steroids, must be on stable (≥7 days) or decreasing dose of steroids.
* Willing and able to provide trial-specific informed consent.
* Willing and able to comply with trial requirements.
* Age ≥16.
* Able to start treatment within 28 days of randomisation.

Exclusion Criteria:

* Pathology inconsistent with IDH WT GBM (e.g. patients with molecular features of PXA or BRAF mutation will be excluded).
* Prior invasive malignancy (except non-melanoma skin cancer), unless disease free for a minimum of one year.
* Prior treatment with stereotactic radiotherapy, brachytherapy or Convection Enhanced Delivery (CED) of any agent.
* Prior treatment, apart from debulking surgery, for first recurrence of GBM.
* Any active co-morbidity making patient unsuitable for trial treatment in the view of the Investigator.
* Personal history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric diagnosis other than depression associated with their underlying glioma condition.
* Prior allergic reaction or significant toxicity (≥Grade 3 CTCAE) related to TMZ treatment.
* Current or recent cannabis or cannabinoid-based medications within 28 days of randomisation and/or unwilling to abstain for the duration of the trial.
* 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.

  o Women of childbearing age must have a negative pregnancy test within 7 days prior to randomisation.
* 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.
* Contra-indication to MRI or gadolinium.
* Hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
* Known hypersensitivity to cannabinoids or excipients of the IMP.
* Known history of current or prior alcohol or drug dependence.
* Known Hepatitis B (HBV), Cytomegalovirus (CMV) or opportunistic infection.
* Has received a live vaccine within 28 days prior to randomisation.
* Unable to administer oromucosal medication due to mucosal lesions or other issues.
* Participation in another therapeutic clinical trial whilst taking part in this trial.
* Any psychological, familial, sociological or geographical condition hampering protocol compliance.

Where this trial is running

Bodelwyddan, Denbighshire and 21 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions GlioblastomaBrain TumorCannabisBrain Tumor, RecurrentcannabinoidGBMtemozolomidesativex
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.