First patient takes part in new Phase 1 clinical trial for patients with recurrent glioblastoma

Treatment sees tumour reduced in size by 50 per cent 

To mark International Brain Tumour Awareness Week, UCLH and The National Brain Appeal are announcing a new clinical trial for patients with recurrent glioblastoma brain cancer. 

Paul, a 62 year old engineer, was diagnosed with glioblastoma brain cancer in December 2023. Following the standard treatment of surgery, radiotherapy and chemotherapy, Paul received the news in July this year that his tumour had become active again. 

Paul is the first patient to be recruited to a new clinical trial that has opened at UCLH. Scans revealed a 50 per cent reduction in his tumour at the end of treatment. 

The trial, CITADEL-123, was designed by UCLH consultant medical oncologist, Dr Paul Mulholland, who is also the chief investigator.  

Patients who have had standard treatment, who now have recurrent disease and are fit and well enough for treatment can undergo resection surgery at The National Hospital for Neurology and Neurosurgery. As much tumour as is safe will be removed and they will then have a small medical device called an Ommaya reservoir implanted under the scalp and this connects via a small tube into the tumour area.  

The tube then allows the nuclear medicine team at University College Hospital to inject the drug - ATT001, Iodine-123 labelled PARP inhibitor - to target the tumour, delivering small amounts of radioactivity. This takes place approximately 14 days after surgery and patients will have weekly injections for 4 to 6 weeks. 

The drug is very potent over short distances, reaching the cancer cell it comes into contact with. The radioactivity should damage and hopefully kill the tumour cells. 

ATT001 delivers its radioisotope payload, Iodine-123, in a highly targeted way to cancer cells expressing PARP, an enzyme they use to repair themselves. This radioisotope emits low energy Auger electrons, which deposit their energy over short distances, making them particularly useful for causing lethal damage to cancer cells while sparing healthy tissue. 

The trial is sponsored by Ariceum Therapeutics, a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, who received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) earlier this year to undertake the Phase 1 clinical trial in patients with recurrent glioblastoma. The project was approved as an Innovative Licensing and Access Pathway (ILAP) project by MHRA.  

The dose escalation study will be followed by expansion cohorts at a recommended dose in monotherapy and in combination with other therapies in recurrent glioblastoma, with the potential to move into primary glioblastoma. 

Ariceum is the first company to sponsor a clinical trial of Auger therapy for recurrent glioblastoma, an aggressive form of brain cancer. 

Dr Mulholland, consultant medical oncologist at UCLH, who leads the Glioblastoma Research Group at the UCL Cancer Institute, said: “We have been working with Ariceum Therapeutics for some years to develop this study. It will allow us to deliver low levels of radioactivity directly into the tumour of patients with recurrent glioblastoma. I’m very pleased that this clinical trial is now open. Potentially this is a very powerful approach and I’m already extremely happy with the results from the first patient. I’m also very proud at how my colleagues in neurosurgery and nuclear medicine have come together as a team to deliver a really novel trial.” 

Dr Austin Smith, consultant medical oncologist at Ariceum Therapeutics, said: “The CITADEL-123 study will allow us to demonstrate the safety and initial efficacy of ATT001 as a potential treatment option to address the high unmet medical need of patients with recurrent glioblastoma.” 

Dr Mulholland’s neurosurgical colleagues at the National Hospital for Neurology and Neurosurgery (NHNN), Ms Huma Sethi, Professor Andrew McEvoy and Ms Anna Miserocchi and nuclear medicine consultant at University College Hospital, Professor Jamshed Bomanji, have all been instrumental in making this trial happen. 

Praising their joint working, medical director of the specialist hospitals board, Dr Tim Hodgson, said: “This trial has been a great team effort of many different specialties across Queen Square and UCLH, coming together to focus on finding new ways of treating glioblastoma.” 

Dr Mulholland is passionate about finding a cure for brain cancer. The National Brain Appeal charity has long-supported his work, providing funding for the UK’s largest-ever immunotherapy trial for brain cancer patients (IPI-GLIO) and funding specialist research posts in his team. 

Dame Siobhain McDonagh MP, who lost her sister, Baroness Margaret McDonagh, to glioblastoma is also supporting Dr Mulholland’s work. Dame Siobhain is calling for a target of getting 200 glioblastoma patients into clinical trials each year; for drugs licensed for other tumours to be trialled on brain tumours; for a requirement that every NHS neuro-oncology multidisciplinary team includes a medical oncologist; and that every NHS doctor training to be a medical oncologist should go through a mandatory course on brain tumours. 

The CITADEL-123 trial will be open for around eighteen months and UCLH is currently the only centre recruiting patients, with other sites due to open at a later date. 

To find out more about the trial and criteria please visit: https://www.isrctn.com/ISRCTN78231121 

Paul’s story 

Paul is a field service engineer in the print industry, maintaining large inkjet printers in the UK and overseas. In early December 2023, he flew to South Korea for work. When the plane landed, he had a very severe headache that he couldn’t shift.

Two weeks later, when he arrived back in the UK, his wife Pauline thought Paul might have had a stroke because his face looked like it had dropped on one side. He was still having the severe headaches. They went to his local A&E where a scan revealed a large mass on his brain. Doctors there contacted The National Hospital for Neurology and Neurosurgery in Queen Square, London, a specialist centre for diseases of the brain and spine. 

Paul was admitted to The National Hospital where consultant neurosurgeon, Ms Huma Sethi, confirmed that he had glioblastoma, a very aggressive form of brain cancer.  

Paul said: “The diagnosis was a huge shock. I’m grateful to the doctors at my local hospital for acting so quickly to get me transferred to Queen Square.” 

He had surgery on 27 December to remove as much of the diseased tissue as possible. He came through the surgery well and was up and walking around the ward the next day. 

Paul said: “I just felt a bit tired after the surgery. My radiotherapy and chemotherapy started soon after and that made me even more tired.” 

Paul had to make adjustments with his employer as he was not able to drive following brain surgery and he had also had a seizure. He now helps to build the printing machines in the company’s factory.  

Paul said: “My employer has been extremely supportive, accommodating and kind. They allowed me the time for all of the treatment and recovery periods over the past eight months. I will be eternally grateful to them and my work colleagues for their support.” 

He continued: “It is good to have some normality and to see people at work, good for my mental well-being. I can get there by train and it was a good excuse to buy a Brompton bike to get me to the factory.” 

Following a scheduled scan, Paul had an appointment with his oncology team. They told him there was recurrence of his tumour, which was difficult news to hear.  

Paul had registered interest in taking part in clinical trials as soon as he was diagnosed.  

By coincidence, the new trial CITADEL-123 was just about to open. Paul met with Dr Paul Mulholland who said he would be eligible to take part. 

He said: “It was good to have another option. I was fully expecting the tumour to return due to its aggressive nature. I know the outcome isn’t great and I was happy to explore anything else. Even if this treatment works, I imagine that it may still reoccur.” 

“This may be the case until a discovery is made to understand what ‘switches’ the glioblastoma cells into a mutation mode.” 

“However, if this trial is successful it would indicate to me that it will now, perhaps, become manageable instead of treatable until the normal expected end of life looms. Allowing sufferers of this disease some hope and longevity.” 

Paul had the surgery to insert the Ommaya reservoir (tube) and has had the weekly injections of the radioactive drug. 

Paul said: “This trial was a lifeline as the likelihood according to the data on survival was a year or less for me and even if it does not directly benefit me, I have the hope that it will feed into the knowledge bank for glioblastoma and other brain cancers and help other sufferers in the future.” 

“I have now had six injections, a week apart. I am delighted to be given the opportunity to be part of this trial and I have not experienced any side-effects from the injections. Possibly a little more tired, but overall, I am feeling very good.” 

He continued: “I’m not frightened by any of this. We are all dealt a hand of cards and you don’t know which ones you are going to get. It will be wonderful if this treatment helps me and if it doesn’t, it doesn’t. I am more than happy, even it if doesn’t benefit me, it may benefit someone else down the line. So I have got nothing to lose and everything to hope for.”