Sativex clinical trials: Phase II Clinical Trial of Cannabis Derivatives
- Official title: ARISTOCRAT: A randomised phase II study of temozolomide with or without cannabinoids in patients with recurrent glioblastoma.
- Lead researcher: Professor Susan Short
- Where: University of Leeds with the University of Birmingham Clinical Trials Unit
- When: 2023
- Cost: £450,000 over 3 years
- Research type: Adult, High Grade, Quality of Life, Clinical, Recurrent Glioblastoma Brain Cancer
- Award type: Clinical Trial
- Website: https://www.birmingham.ac.uk/research/crctu/trials/aristocrat/index.aspx
The trial is now open in some of the participating hospitals. For the most up-to-date information about the recruitment locations, please visit the clinical trials website.
Sativex clinical trials
Here we look at a Sativex clinical trial that aims to understand whether adding cannabis derivatives to chemotherapy drug temozolomide can help people affected by brain tumours live longer, better lives.
On this page, we’ll cover:
- Phase I of the Sativex clinical trial
- Phase II of the Sativex clinical trial
- What does the trial hope to find out?
- Why are Sativex clinical trials important?
- Who will the trial help?
What happened in phase I of the Sativex clinical trial?
Cannabis-like drugs (cannabinoids aka cannabis derivatives) have well described effects in the brain. Primary brain tumours, including glioblastoma (GBM), have been shown to have receptors to cannabinoids on their cell surface. This suggests that they may respond to these drugs. Laboratory studies on brain tumour cells treated with cannabinoids have already shown that these drugs may slow brain tumour growth and that they may work particularly well when used with temozolomide.
A phase I study led by Professor Susan Short, showed that the addition of a drug called nabiximols (also known as Sativex), which is a specific combination of cannabinoids given in the form of an oral spray, to standard of care treatment with temozolomide, was feasible and well tolerated by people with recurrent GBM. The researchers also observed that more patients were alive after one year in the nabiximols arm compared to the placebo arm, however the trial was too small to be able to confirm a survival benefit.
What is phase II of the Sativex clinical trial?
This phase II clinical trial will explore whether combining nabiximols (also known as Sativex) with temozolomide works better than using temozolomide alone and whether participants receiving nabiximols live longer, better lives.
To do this they have planned a randomised, placebo-controlled clinical trial. A randomised controlled trial is where people are put into groups by chance, and placebo-controlled means that not everyone will receive the cannabinoid treatment. This means the effect of the additional cannabinoid treatment will be clearer.
In this trial participants with recurrent GBM will be divided into two groups, one group (2/3 of participants) will be given temozolomide plus nabiximols and the second group (1/3 of participants) will be given temozolomide plus a placebo. The experiences of these two groups will then be compared.
People will be selected for each group by a computer. Neither the participant, nor the treating team, can choose or will be aware of which treatment individual participants are receiving.
What does the Sativex clinical trial hope to find out?
The main aim of the trial is to find out whether patients receiving nabiximols with temozolomide live longer, on average than those receiving temozolomide plus placebo.
We also want to find out how patients taking nabiximols plus temozolomide feel compared to those receiving temozolomide plus placebo in terms of their quality of life. All participants on the trial will receive regular follow up including clinical assessment, blood tests, MRI scans, and they will be asked to complete quality of life questionnaires.
The centres participating in the trial are in Leeds, Birmingham, London (2 centres), Cambridge, Edinburgh, Glasgow, Liverpool, Manchester, Nottingham, Oxford, Southampton, Bristol and Cardiff.
For more information about cannabis derivatives please see our dedicated information page
A message from Peter Buckle, the Patient Advocate Co-applicant on the trial
“Any one who has witnessed the horror of having a loved one suffer from a brain tumour will fully understand the need for clinical trials to find improved treatments. My wife Wendy died aged 54 after an illness of less than six months. It is not just the short survival time that typifies this disease, it is also the rapid and severe onset of disability caused not just by the tumour progression but also by the serious side effects of current treatments.
This ARISTOCRAT clinical trial is a novel approach and has the potential to give better outcomes to certain patients – those whose tumour recurs after their standard treatment.
After Wendy died, I started to become involved with research projects as a patient advocate, helped enormously by The Brain Tumour Charity.
Every clinical trial in the UK is required to include a patient advocate as a co-applicant. I feel privileged to have been invited to undertake this role for ARISTOCRAT. Obviously I wish the trial every success – and would encourage everyone please to contribute to the fundraising.”
Why are Sativex clinical trials important?
Treating people with GBM remains extremely challenging. Even with the best treatments we have (surgery followed by radiotherapy and chemotherapy), nearly all of these tumours re-grow quickly. Unfortunately, there are very few treatment options once this occurs. Most commonly in this setting, people are treated with chemotherapy (often temozolomide), however the impact on survival is small, even in people with tumours that initially respond. New treatments to improve this poor outlook are badly needed.
Who will the trial help?
In the short term we expect the trial to help all enrolled participants. There is research that shows that even if someone is receiving a placebo they benefit from the dedicated follow up during a study like this.
In the long term we hope to show that cannabis derivatives are a good treatment option that improve both the length and quality of survival for people with a recurrent GBM.
If the outcome of this trial is positive, then researchers would likely expand the investigation to include people newly diagnosed with a glioblastoma, and other types of brain tumour.
Milestone 1: Getting the funds to back the trial!
We launched an appeal to raise the £450,000 needed to open the trial as soon as possible, thank you to everyone that donated and helped us to reach our target.
For years we’ve heard stories of how cannabis or CBD oil is being used in the community. But, to date, the evidence needed to get it accepted into routine clinical practice has been mixed. To change this we’ve worked with our research community to figure out how to test this in a clinical setting.
Milestone 2: Progressing through the regulatory process and opening the trial
Regulatory approvals are complete. The first trial centre opened at Leeds Teaching Hospitals NHS Trust in February 2023, shortly followed by The Christie NHS Foundation Trust in April 2023.
Milestone 3: Recruiting the 40 people what will participate in the pilot phase of the trial
Milestone 4: Achieving a go/no-go point based on the data of the pilot phase
(Milestone 4a: Opening recruitment to an additional 192 people in the next phase of the trial)
Milestone 5: Assessing all the information available and making a recommendation on the use of cannabis derivatives in the clinical treatment of glioblastoma, initially, and other types of brain tumour.
Frequently Asked Questions about the Sativex clinical trial
When centres are open for recruitment, your treating oncologist will be aware of the study if it is open in your hospital. Or they can refer you to a treating centre if necessary. The centres that currently plan to participate in the trial are listed below, though they won’t all be opening at once:
- Queen Elizabeth Hospital Birmingham, Birmingham
- Bristol Haematology & Oncology Centre, Bristol
- Addenbrooke’s Hospital, Cambridge
- Velindre Cancer Centre, Cardiff
- Western General Hospital, Edinburgh
- Beatson West of Scotland Cancer Centre, Glasgow
- St James’s University Hospital, Leeds
- Guy’s Hospital, Guy’s and St Thomas’, London,
- Charing Cross Hospital, London,
- The Christie Hospital, Manchester
- City Hospital, Nottingham
- John Radcliffe Hospital, Oxford
- Southampton General Hospital, Southampton
- Clatterbridge Cancer Centre, Wirral
Trial participants must be over 16 years old and have an MGMT promotor methylated, IDH wild type (WT) GBM which has recurred for the first time. There are additional inclusion and exclusion criteria for the trial which your treating oncologist should be able to discuss with you.
Nabiximols (Sativex) is a Class B controlled drug that can be prescribed legally in the UK by specialist doctors in certain circumstances for medicinal use. Aside from within this clinical trial setting, it is already licensed for use on the NHS as a treatment for certain patients with multiple sclerosis.
It is a Class B controlled drug under the Misuse of Drugs Act 1971 and is a Schedule 4 controlled drug under the Misuse of Drug Regulations 2001. It was moved to Schedule 4 following its marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA). This means it can be prescribed legally in the UK with no restrictions on supply, recording, storage or destruction.
Cannabis itself and cannabis oil are also classified as class B drugs in the UK because they contain the component THC. It is illegal to possess or supply them. However, since 1 November 2018, cannabis-based products for medicinal use have been available in the UK in certain circumstances only.
CBD oil is different from cannabis oil because it does not contain THC. It is currently legal in the UK – as long as it has been produced from an EU-approved strain of hemp and as long as it is marketed as a food supplement without any medicinal claims. You can buy it in many high street health food shops.
You can read more about the difference between cannabis, cannabis oil and CBD oil here.
Not yet. Most of the research to date has been done on cells in the lab, with some evidence suggesting that cannabis-derived compounds can kill glioma tumour cells and that they may be effective when given alongside temozolomide chemotherapy.
Earlier this year, Professor Susan Short led a small study where researchers assessed cannabis-based drug Sativex (given through an oral spray) for patients whose glioblastoma tumours had grown back after initial therapy. They used this alongside temozolomide chemotherapy and showed that it was feasible to give this treatment combination and that it could be tolerated by patients.
Phase 1 trial led by Susan Short using Sativex. Find out more about this trial here.
While we don’t yet know whether cannabinoids can help treat brain tumours, the cannabis-based drug Nabilone can be legally prescribed to help relieve symptoms such as chemotherapy-induced nausea and vomiting. You can read more about this here.
The trial aims to compare the effects of temozolomide plus a cannabis-based drug (nabiximols) against temozolomide with a placebo (non-active drug) to see if patients treated with nabiximols plus temozolomide live longer. It will also assess how patients feel on the treatment and how it affects their quality of life.
The trial will take around three years to reach the point where it has recruited and followed up enough patients to give conclusive results about the effects of adding nabiximols to temozolomide.
We have further information about cannabinoids and additional FAQs on our cannabinoids information and support page.
More information about the trial can be found on the University of Birmingham website.