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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
Oromucosal spray
Oral capsule
Nabiximols-matched placebo oromucosal spray
Overall survival time (OS)
To establish whether the addition of cannabinoids (Nabiximols) to standard TMZ treatment improves overall survival time (OS) in MGMT methylated recurrent GBM compared to the addition of placebo to TMZ.
Time frame: Time in whole days from date of randomisation to the date of death from any cause, assessed at a minimum of 12 months..
Overall survival at 12 months (OS12) (and 6 and 24 months)
Of particular clinical relevance is the overall survival at 12 months from date of randomisation, i.e. whether the participant is alive or not at that time point. Overall survival at 6 months and 24 months will also be of interest.
Time frame: 6, 12 and 24 months
Progression-free survival time (PFS)
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. PFS includes radiological progression assessed in accordance with RANO criteria and clinical progression where radiological progression is not possible.
Time frame: 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), whichever came first, assessed at a minimum of 12 months.
Health-related quality of life (HRQoL) as assessed by EORTC QLQ-C30
Generic Health-related quality of life (HRQoL) will be assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) consisting of function, symptom and global health status scales, scored 1-4 with lower scores indicating better outcomes..
Time frame: Baseline (Week 0), Week 8, Week 16, End of Treatment (Week 24)
Adverse events
Assessment of AEs according to the current NCI-CTCAE v5.0 criteria. Acute AE will be defined as those occurring up to 12 weeks post-end of treatment. Late AE will be defined as those occurring after 12 weeks post-end of treatment. The end of treatment will be the date of the final chemotherapy cycle.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Glan Clwyd Hospital
Bodelwyddan, Denbighshire, United Kingdom
NOT_YET_RECRUITINGMount Vernon Hospital, The Hillingdon Hospitals NHS Foundation Trust
Northwood, Middlesex, United Kingdom
RECRUITINGAberdeen Royal Infirmary, NHS Grampian
Aberdeen, United Kingdom
RECRUITINGBelfast City Hospital, Belfast Health and Social Care Trust
Belfast, United Kingdom
WITHDRAWNQueen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
RECRUITINGBristol Haematology & Oncology Centre, University Hospitals Bristol & Weston NHS Foundation Trust
Bristol, United Kingdom
ACTIVE_NOT_RECRUITINGAddenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom
RECRUITINGVelindre Cancer Centre, Velindre University NHS Trust
Cardiff, United Kingdom
RECRUITINGWestern General Hospital, NHS Lothian
Edinburgh, United Kingdom
WITHDRAWNBeatson West of Scotland Cancer Centre, NHS Greater Glasgow & Clyde
Glasgow, United Kingdom
WITHDRAWN...and 12 more locations
Time frame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 16, Week 20, End of Treatment (Week 24)