A dose-finding study of the safety and tolerability of intravenous reovirus (REOLYSIN®)(pelareorep) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with standard of care chemoradiotherapy /adjuvant chemotherapy for Glioblastoma Multiforme (GBM)
University of Leeds
Duration of Study in the UK
1 years, 9 months, 1 days
Summary of Research
This study will assess the safety and tolerability of the reovirus (REOLYSIN®) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with standard of care chemoradiotherapy and adjuvant chemotherapy in adult patients with glioblastoma multiforme (GBM).
Currently, patients with GBM receive debulking surgery followed by 6 weeks of chemoradiotherapy with concurrent chemotherapy for 6 months. This study will look at combining this current treatment with Reolysin and GM-CSF as previous studies have demonstrated tolerability of the virus with chemotherapy with early evidence of anti-tumour activity. Preclinical data also supports the addition of GM-CSF as it has been demonstrated it increases the number of white blood cells which are used to protect and transport the virus to the tumour therefore ensuring the virus reaches the cancer cells.
There are two parts to this study; a dose escalation phase and a non-randomised expansion phase.
In the dose escalation phase, six patients will be treated per cohort in order for any toxicities to be observed. Once the first six patients have been treated and their data reviewed, it will be decided whether to increase or decrease the dose for the next six patients depending on the toxicity observed. Once the safest dose is found this will be used to treat an additional 12 patients in the expansion phase.
All patients, whether in the escalation phase or expansion phase, will receive six weeks of chemoradiotherapy followed by six months of adjuvant chemotherapy as they would if they were not participating in this study. They will then receive GM-CSF and Reolysin during weeks 1 and 4 of chemoradiotherapy and for one week each month during adjuvant chemotherapy.
The study will take place in five hospitals and recruit up to 24 patients.
Summary of Results
The research team found that pelareorep didn’t cause too many serious side effects. It may be a useful treatment for glioblastoma.
This study was for people who had a high grade brain tumour called a glioblastoma (GBM). People who took part had already had surgery to remove their brain tumour. You couldn’t take part if you’d had any other treatment.
The first few people who took part had a lower dose of pelareorep. As they had no serious side effects, the next few people who took part had a higher dose. This is called a dose escalation study. Researchers give new treatments in this way to find the best dose to give.
A total of 17 people joined this trial: 8 in the group who had the lower dose of pelareorep, and 9 in the group who had the higher dose of pelareorep.
The research team were able to look at the side effects for 15 people who took part: 7 people who had the lower dose and 8 people who had the higher dose.
Everyone taking part had at least 1 side effect. But some were due to the temozolomide or the radiotherapy. They weren’t all due to pelareorep. And some were mild or didn’t last long.
They found that pelareorep didn’t cause too many serious side effects. The most common of the more serious side effects were fever and flu like symptoms.
Only 1 person had a side effect that was serious enough to suggest the dose they had was a bit high. They were in the higher dose group and had a significant drop in blood pressure.
How well treatment worked:
The team looked at how well the treatment worked for 12 people who took part: 6 who had the lower dose and 6 who had the higher dose.
They looked at how long it was before people’s cancer started to grow. They found it was: 7.8 months for everyone taking part; 6.1 months for those who had the lower dose of pelareorep; and 9.4 months for those who had the higher dose of pelareorep.
They also looked at whether the brain tumour had responded to treatment, in 11 people who took part. They found that for 5 people who had the lower dose of pelareorep, the brain tumour: didn’t get smaller in anyone; stayed the same in 3 people; and continued to grow in 2 people.
And for 6 people who had the higher dose of pelareorep, the brain tumour: got a bit smaller in 3 people; stayed the same in 1 person; and continued to grow in 2 people.
They also looked at how long people survived: 13.1 months for everyone taking part; 12.6 months for those who had the lower dose of pelareorep; and 16.1 months for those who had the higher dose of pelareorep.
The research team concluded that pelareorep didn’t cause too many serious side effects. And that it might be a useful treatment for people with glioblastoma (GBM).
They suggest other trials are done to find out more about how well pelareorep works for GBM and for other cancers.
East of England - Cambridge East Research Ethics Committee
Date of REC Opinion
22 Dec 2016
Further Information Favourable Opinion