Cannabinoid-Based Brain Tumor Drug Study Begins

Patients with aggressive brain tumors may be allowed to participate in a new trial of a cannabinoid-based medication coordinated by the University of Birmingham.

A significant UK clinical trial of an oral spray containing cannabis to treat recurrent glioblastoma has begun at two sites in the UK. ARISTOCRAT, a three-year phase II trial funded by The Brain Tumour Charity and coordinated by the Cancer Research UK Clinical Trials Unit at the University of Birmingham, will look into whether combining nabiximols and chemotherapy can help extend the lives of people with recurrent glioblastoma.

Anyone interested in participating in this study should first consult with their medical team to determine that they are eligible.

In 2023, it plans to recruit more than 230 glioblastoma patients at 14 NHS institutions in England, Scotland, and Wales, including Birmingham, Bristol, Cambridge, Cardiff, Edinburgh, Glasgow, London, Liverpool (Wirral), Manchester, Nottingham, Oxford, and Southampton.

Professor Pamela Kearns, Director of the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham, which is co-ordinating the trial, said:

“ARISTOCRAT represents a significant step in our journey towards finding safe and effective treatments for the most aggressive brain tumours. By testing innovative combinations of drugs we hope to improve the outcome for this challenging disease.

“We’re immensely proud to be able to bring this trial to patients with the support of the Brain Tumour Charity and thanks to the generosity of all those who gave to the crowdfunding campaign.”

Glioblastoma

Glioblastoma is the most aggressive type of brain cancer, with a recurrent survival rate of fewer than 10 months.

A phase I clinical research including 27 patients in 2021 discovered that nabiximols might be tolerated in combination with chemotherapy and has the potential to extend the lives of those with recurrent glioblastoma.

If the experiment is successful, experts believe that nabiximols will be a new and exciting addition to NHS treatment for glioblastoma patients since temozolomide chemotherapy was introduced in 2007.

In August 2021, The Brain Tumour Charity’s fundraising appeal, backed by Olympic champion Tom Daley, raised the £450,000 needed for this phase II trial in just three months, and Jazz Pharmaceuticals has generously agreed to provide nabiximols and matched placebo to patients on the ARISTOCRAT trial for free.

Participants will self-administer nabiximols or a placebo spray and will be monitored by the clinical study team on a regular basis, including blood tests and MRI scans. This will also be one of the first trials to incorporate The Brain Tumour Charity’s BRIAN app.

“We are delighted to announce that, thanks to the support and generosity of so many in the brain tumour community, the ARISTOCRAT trial has recruited its first patients.

“We are really excited that this world-first trial, being run here in the UK, could help accelerate a cure for this devastating disease.

“In the last decade there has been significant interest from both patients and researchers about the potential for cannabinoids to treat glioblastomas and we are so grateful to everyone across the world who helped to fund such an important study.

“The early-stage findings were really promising and we now look forward to understanding whether adding nabiximols to chemotherapy could help improve quality of life and extend life for those affected by a glioblastoma diagnosis. We hope that this will offer the first new drug to treat glioblastoma in over 15 years.

“In the meantime, while other cannabinoid-based products may help alleviate symptoms, there is insufficient evidence to recommend their use to help treat brain tumours. For anyone considering using cannabinoid-based products or other complementary therapies, it’s vital that you discuss these with your medical team first, as they could interact with other treatments such as anti-epileptic medicines or steroids.”

The ARISTOCRAT trial aims to meet an unmet need for those with recurrent glioblastoma because there are relatively few therapeutic options available after recurrence. Laura Smallbone’s husband, Peter, died on July 8, 2022, after his glioblastoma recurred and no more therapeutic options were available.

Peter Smallbone, 47, died barely 15 months after being diagnosed with glioblastoma, leaving behind his two young children, aged 9 and 11, and his wife Laura.

Laura said: “When Pete was diagnosed with a glioblastoma in April 2021, the prognosis was poor, we knew it couldn’t be cured, but we knew we could fight it. When it recurred, Pete had surgery, but there were no other treatment options for us – there needs to be a better roadmap for recurrence”.

Peter was an active father of two and had very few symptoms in the lead up to his brain tumour diagnosis.

Laura said: “Pete suffered from the odd headache, but he just took paracetamol and he was fine. Just the day before being admitted into hospital over the Easter weekend, he had taken our children to football practice.”

“There were other signs that, in hindsight, were linked to Pete’s brain tumour. His personality changed, which we now know was due to the tumour being in the right frontal lobe. He began to obsessively buy lots of tickets for things, such as gigs, sometimes two on the same night. He also began to question how happy he was with his life and could say mean things to me and the children which was very unlike him. He was a very loving husband and dad.”

“OK – So, what do we do now?”

On Saturday, Peter felt quite fatigued, but as the day progressed, he began vomiting and staggering while walking. Laura called NHS 111, who advised him to go to A&E, but by the time Laura was about to go, Peter couldn’t remember how to dress himself, so she called an ambulance.

Peter was promptly transferred to Birmingham’s Queen Elizabeth Hospital for a CT scan.

Laura said: “The doctors said that they had found a mass and that it was likely to be cancer. It was a very difficult time as I couldn’t be at the hospital with him due to all of the COVID restrictions.”

Peter had surgery the following day, Easter Sunday. The debulking surgery was successful, and the 8cm tumor in Peter’s brain was removed. The tumor was diagnosed as a glioblastoma, and a grueling program of radiotherapy and chemotherapy ensued.

Laura said “It was hard not seeing my husband for a week following his diagnosis and surgery. It was also difficult having to have many of our consultations over the phone because of the pandemic.

“There was a sense of frustration because we had to fight so hard to get Pete the care he needed. Communicating with different sectors of the NHS was difficult, and I would like to see that improved in the future. Having to explain our situation over and over to different people was very hard. We also had a fight for end of life care for Pete.”

Peter had numerous rounds of treatment that initially worked, and the family was able to enjoy the summer of 2021 and make many memories together. However, routine tests later that year revealed that the tumor had returned, and Peter underwent surgery just before Christmas 2021. However, the tumor had grown again barely 8 weeks later, and there were no additional therapy alternatives available.

Laura said: “We sought second opinions, we tried all the options given to us, but after Pete’s tumour grew back, we were told there was nothing else that could be done. I was caring for him at home with the support of carers and after several falls he went into a hospice. The hospice was peaceful, and the whole family were able to visit him – even the dog. A few weeks after going into the hospice, Pete died, aged just 47.

“This has been really hard for the family, especially our two young children. Pete was absolutely determined to make the most of what he had, and do all the fun things for as long as he could. Losing him bit-by-bit to this cruel disease was difficult, and I’d really like to see more options for families like ours. For 15 months we were asking ourselves ‘OK, so now what do we do?’ – there needs to be more treatment options for people diagnosed with a glioblastoma. There also needs to be more awareness of the disease so that there is a greater understanding of what families like ours had to face.”

Principal Investigator, Professor Susan Short, Professor of Clinical Oncology and Neuro-Oncology at the University of Leeds, said:

“We are very excited to open this trial here in Leeds and very much look forward to running the study which will tell us whether cannabinoid- based drugs could help treat the most aggressive form of brain tumour.

“The treatment of glioblastomas is extremely challenging. Even with surgery, radiotherapy and chemotherapy, nearly all of these brain tumours re-grow within a year, and unfortunately there are very few options for patients once this occurs.

“Cannabinoid-based drugs have well-described effects in the brain and there has been a lot of interest in their use across different cancers for a long time now. Glioblastomas have receptors to cannabinoids on their cell surface, and laboratory studies on glioblastoma cells have shown these drugs may slow tumour growth and work particularly well when used with temozolomide.

“We now have the opportunity to take these laboratory results, and those from the phase I trial and investigate whether this drug could help glioblastoma patients live longer in this first-of-a-kind randomised clinical trial.”

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