ARISTOCRAT: Blinded Trial of Temozolomide +/- Cannabinoids
ARISTOCRAT
A Randomised Controlled Phase II Trial of Temozolomide With or Without Cannabinoids in Patients With Recurrent Glioblastoma
3 other identifiers
interventional
120
1 country
22
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2023
Typical duration for phase_2
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 7, 2022
CompletedFirst Posted
Study publicly available on registry
November 29, 2022
CompletedStudy Start
First participant enrolled
February 3, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2027
May 5, 2026
April 1, 2026
3.6 years
November 7, 2022
April 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 in whole days from date of randomisation to the date of death from any cause, assessed at a minimum of 12 months..
Secondary Outcomes (4)
Overall survival at 12 months (OS12) (and 6 and 24 months)
6, 12 and 24 months
Progression-free survival time (PFS)
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
Baseline (Week 0), Week 8, Week 16, End of Treatment (Week 24)
Adverse events
Baseline (Week 0), Week 4, Week 8, Week 12, Week 16, Week 20, End of Treatment (Week 24)
Study Arms (2)
Standard Temozolomide with Nabiximols
EXPERIMENTAL* Temozolomide 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. * Nabiximols up to 12 oromucosal sprays per day up to a maximum of 6 cycles; self titrated over days 1-14 in cycle 1.
Standard Temozolomide with Nabiximols-matched placebo
PLACEBO COMPARATOR* Temozolomide 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. * Nabiximols-matched placebo up to 12 oromucosal sprays per day up to a maximum of 6 cycles; self titrated over days 1-14 in cycle 1.
Interventions
Oral capsule
Nabiximols-matched placebo oromucosal spray
Eligibility Criteria
You may qualify if:
- 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.
- +5 more criteria
You may not qualify if:
- 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.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Leedscollaborator
- The Brain Tumour Charitycollaborator
- Jazz Pharmaceuticalscollaborator
- University of Birminghamlead
Study Sites (22)
Glan Clwyd Hospital
Bodelwyddan, Denbighshire, LL18 5UJ, United Kingdom
Mount Vernon Hospital, The Hillingdon Hospitals NHS Foundation Trust
Northwood, Middlesex, HA6 2RN, United Kingdom
Aberdeen Royal Infirmary, NHS Grampian
Aberdeen, AB25 2ZN, United Kingdom
Belfast City Hospital, Belfast Health and Social Care Trust
Belfast, BT9 7AB, United Kingdom
Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2TH, United Kingdom
Bristol Haematology & Oncology Centre, University Hospitals Bristol & Weston NHS Foundation Trust
Bristol, BS2 8ED, United Kingdom
Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ, United Kingdom
Velindre Cancer Centre, Velindre University NHS Trust
Cardiff, CF15 7QZ, United Kingdom
Western General Hospital, NHS Lothian
Edinburgh, EH4 2XU, United Kingdom
Beatson West of Scotland Cancer Centre, NHS Greater Glasgow & Clyde
Glasgow, G12 0YN, United Kingdom
Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust
Hull, HU16 5JQ, United Kingdom
St James's University Hospital, Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF, United Kingdom
St Bartholomew's Hospital, Barts Health NHS Trust
London, EC1A 7BE, United Kingdom
Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT, United Kingdom
Charing Cross Hospital, Imperial College Healthcare NHS Trust
London, W6 8RF, United Kingdom
Maidstone Hospital, Maidstone and Tunbridge Wells NHS Trust
Maidstone, ME16 9QQ, United Kingdom
The Christie Hospital, The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Clatterbridge Cancer Centre, The Clatterbridge Cancer Centre NHS Foundation Trust
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
City Hospital, Nottingham University Hospitals NHS Trust
Nottingham, NG5 1PB, United Kingdom
Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU, United Kingdom
Derriford Hospital, University Hospitals Plymouth NHS Trust
Plymouth, PL6 8DH, United Kingdom
Southampton General Hospital, University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD, United Kingdom
Related Publications (1)
Bhaskaran D, Savage J, Patel A, Collinson F, Mant R, Boele F, Brazil L, Meade S, Buckle P, Lax S, Billingham L, Short SC. 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. 2024 Jan 15;24(1):83. doi: 10.1186/s12885-023-11792-4.
PMID: 38225549BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fiona Collinson, MBBS, BSc, MRCP, FRCR, PhD
University of Leeds
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 7, 2022
First Posted
November 29, 2022
Study Start
February 3, 2023
Primary Completion (Estimated)
September 1, 2026
Study Completion (Estimated)
April 1, 2027
Last Updated
May 5, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
Scientifically sound proposals from appropriately qualified researchers will be considered for data sharing. Requests should be made by returning a Data Sharing Request Form to newbusiness@trials.bham.ac.uk; this captures the research requirements, statistical analysis plan, and intended publication schedule. Requests will be reviewed by the Cancer Research UK Clinical Trials Unit (CRCTU) Directors in discussion with the Chief Investigator (CI), Trial Management Group (TMG) and independent Trial Steering Committee (TSC). They will consider the scientific validity of the request, qualifications of the researchers, views of CI, TMG and TSC, consent arrangements, practicality of anonymizing the requested data contractual obligations. If supportive of the request, and where not already obtained, Sponsor consent for data transfer will be sought before notifying applicants of the outcome. It is anticipated that applicants will be notified within 3 months of receipt of the original request.