Trial Title:
ARISTOCRAT: Blinded Trial of Temozolomide +/- Cannabinoids
NCT ID:
NCT05629702
Condition:
Glioblastoma
Brain Tumor
Cannabis
Brain Tumor, Recurrent
Conditions: Official terms:
Glioblastoma
Brain Neoplasms
Recurrence
Temozolomide
Nabiximols
Dronabinol
Cannabidiol
Conditions: Keywords:
cannabinoid
GBM
temozolomide
sativex
nabiximols
cannabis
glioblastoma
brain
recurrent
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
Nabiximols
Description:
Oromucosal spray
Arm group label:
Standard Temozolomide with Nabiximols
Other name:
Sativex
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Oral capsule
Arm group label:
Standard Temozolomide with Nabiximols
Arm group label:
Standard Temozolomide with Nabiximols-matched placebo
Intervention type:
Drug
Intervention name:
Nabiximols-matched placebo
Description:
Nabiximols-matched placebo oromucosal spray
Arm group label:
Standard Temozolomide with Nabiximols-matched placebo
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).
Detailed description:
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 234 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 current phase II trial design will enable potential expansion of recruitment into a
phase III trial, should the emerging phase II results warrant this development.
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.
Criteria for eligibility:
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
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.
- 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 SD (or PR/CR) at the end of first-line treatment.
- ≥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 (on original pathology) 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 30 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.
Gender:
All
Minimum age:
16 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mount Vernon Hospital, The Hillingdon Hospitals NHS Foundation Trust
Address:
City:
Northwood
Zip:
HA6 2RN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Thomas Carter
Facility:
Name:
Aberdeen Royal Infirmary, NHS Grampian
Address:
City:
Aberdeen
Zip:
AB25 2ZN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Rafael Moleron
Facility:
Name:
Belfast City Hospital, Belfast Health and Social Care Trust
Address:
City:
Belfast
Zip:
BT9 7AB
Country:
United Kingdom
Status:
Withdrawn
Facility:
Name:
Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Foundation Trust
Address:
City:
Birmingham
Zip:
B15 2TH
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Sara Meade
Facility:
Name:
Bristol Haematology & Oncology Centre, University Hospitals Bristol & Weston NHS Foundation Trust
Address:
City:
Bristol
Zip:
BS2 8ED
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Christopher Herbert
Facility:
Name:
Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
Address:
City:
Cambridge
Zip:
CB2 0QQ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Fiona Harris
Facility:
Name:
Velindre Cancer Centre, Velindre University NHS Trust
Address:
City:
Cardiff
Zip:
CF15 7QZ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Jillian MacLean
Facility:
Name:
Western General Hospital, NHS Lothian
Address:
City:
Edinburgh
Zip:
EH4 2XU
Country:
United Kingdom
Status:
Withdrawn
Facility:
Name:
Beatson West of Scotland Cancer Centre, NHS Greater Glasgow & Clyde
Address:
City:
Glasgow
Zip:
G12 0YN
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Stefan Nowicki
Facility:
Name:
Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust
Address:
City:
Hull
Zip:
HU16 5JQ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Sanjay Dixit
Facility:
Name:
St James's University Hospital, Leeds Teaching Hospitals NHS Trust
Address:
City:
Leeds
Zip:
LS9 7TF
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Fiona Collinson
Facility:
Name:
St Bartholomew's Hospital, Barts Health NHS Trust
Address:
City:
London
Zip:
EC1A 7BE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Rachel Lewis
Facility:
Name:
Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust
Address:
City:
London
Zip:
SE1 9RT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Lucy Brazil
Facility:
Name:
Charing Cross Hospital, Imperial College Healthcare NHS Trust
Address:
City:
London
Zip:
W6 8RF
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Matthew Williams
Facility:
Name:
Maidstone Hospital, Maidstone and Tunbridge Wells NHS Trust
Address:
City:
Maidstone
Zip:
ME16 9QQ
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Samantha Forner
Facility:
Name:
The Christie Hospital, The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Catherine McBain
Facility:
Name:
City Hospital, Nottingham University Hospitals NHS Trust
Address:
City:
Nottingham
Zip:
NG5 1PB
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Karen Foweraker
Facility:
Name:
Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
Address:
City:
Oxford
Zip:
OX3 9DU
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Juliet Brock
Facility:
Name:
Derriford Hospital, University Hospitals Plymouth NHS Trust
Address:
City:
Plymouth
Zip:
PL6 8DH
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Elizabeth Lim
Facility:
Name:
Southampton General Hospital, University Hospital Southampton NHS Foundation Trust
Address:
City:
Southampton
Zip:
SO16 6YD
Country:
United Kingdom
Status:
Withdrawn
Facility:
Name:
Clatterbridge Cancer Centre, The Clatterbridge Cancer Centre NHS Foundation Trust
Address:
City:
Wirral
Zip:
CH63 4JY
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Shaveta Mehta
Start date:
February 3, 2023
Completion date:
February 2027
Lead sponsor:
Agency:
University of Birmingham
Agency class:
Other
Collaborator:
Agency:
University of Leeds
Agency class:
Other
Collaborator:
Agency:
The Brain Tumour Charity
Agency class:
Other
Collaborator:
Agency:
Jazz Pharmaceuticals
Agency class:
Industry
Source:
University of Birmingham
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05629702
https://www.birmingham.ac.uk/aristocrat
