EORTC 1709-BCG
Research type
Research Study
Full title
A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma.
IRAS ID
243129
Contact name
Lucy Brazil
Contact email
Sponsor organisation
European Organisation for research and Treatment of cancer (EORTC)
Eudract number
2017-003908-50
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 0 months, 30 days
Research summary
Summary of Research
This study is for adults who have newly diagnosed glioblastoma (a type of brain cancer) and have received surgery. The purpose of the study is to find out whether giving the drug marizomib in combination with standard treatment (radiotherapy and temozolomide) is better than standard treatment alone. This is measured by the length of time that participants live (overall survival).\n\nGlioblastoma is the most common and malignant primary brain tumour in adults and its incidence is increasing. New therapies are needed as results achieved with traditional cancer therapies are poor due to glioma cell resistance to irradiation and chemotherapy. Marizomib has been investigated as potentially beneficial drug in glioblastoma patients and this study builds on the encouraging observations seen in clinical trials. \n\nThe study will compare the effects of marizomib using clinical examinations, regular scans and blood tests. The study has a translational research component where tumour and blood samples will also be analysed to understand the effects of the drug.\n\nThis study will take place in NHS sites in the UK as part of a wider international study. The study is sponsored and coordinated by the EORTC (European Organisation for Research and Treatment of Cancer), a non-profit organisation based in Brussels.
Summary of Results
This trial looked at marizomib for people who have the most common type of brain cancer: glioblastoma, a fast growing type of (malignant) brain tumour.
It was for people whose cancer was just diagnosed. Standard treatment is available for such people and involves a combination of surgery, radiation therapy (RT), and a drug called temozolomide (TMZ).
This trial was open for people to join between 03/08/2018 and 21/09/2020. The trial team published results at the ASCO congress in 2021. The final results will be published at the end of year 2023.More about this trial
Marizomib is a type of targeted drug called a cancer growth blocker. It stops the signals that cells use to divide and grow. Researchers thought that adding marizomib to the standard treatment might help in delaying the growth of the cancer, prolonging life and/or improving quality of life.
Genes are coded messages that tell cells how to behave. Sometimes genes have changes (methylation) in the code. This can affect how cells behave and how cancer treatments work.
Researchers thought that marizomib might work better for cancer cells that don’t have a change on genes called MGMT methylation (they are called uMGMT tumours). But they weren’t sure so wanted to find out more.
The main aims of the trial were to find out:
• Whether the addition of marizomib prolongs survival
• Whether the addition of marizomib delays the further growth of the cancer
• Whether the addition of marizomib is safe and the side effects are tolerable
• Whether marizomib improves quality of life or impacts how the brain works
The trial also collected information on how marizomib works in the body when given together with the standard of care.Summary of results
A total of 749 people joined this trial, from 80 institutions in 12 countries. The researchers have the results for all patients. As seen in other research, 59% of patients had a tumour without MGMT methylation.Trial design
This was a phase 3 trial. One in 2 study participants received marizomib in addition to the standard treatment for as long as it worked and the side effects weren’t too bad.The team followed up everyone for about 28 months.
After that time the team looked at the duration people lived for. On average this was:
- about 15 months for people who received standard treatment
- about 16 months for people who received standard treatment plus marizomib In people with an uMGMT tumour, on average this was:
- about 14 months for people who received standard treatment
- about 15 months for people who received standard treatment plus marizomib After 28 months, the team also looked at the duration of people living without signs of their cancer getting worse. On average this was 6 months for both treatments.
In summary, marizomib did not help prolong life or delay cancer growth.Side effects
The trial team looked at the severe side effects when adding marizomib to the standard treatment. In summary, people who received marizomib in addition to standard treatment had similar side effects in the mid-term and worse side effects in the long term, than those who received standard treatment.
The most common severe side effects included:
• Ataxia, a condition where people have trouble controlling their arms and legs
• Swelling of the brain
• Seizure, a sudden surge of electrical activity in the brain that can cause convulsions and a loss of consciousness
A total of 8 people died from side effects of the treatment, among those who received marizomib in addition to the standard treatment.
Detailed results have been published on the EUDRACT website (EudraCT 2017-003908-50).
There were too few samples and data collected to allow researchers to draw any conclusions on how marizomib works in the body when given together with the standard of care.
Finally, people who received marizomib in addition to standard treatment had worse psychological health status and their brain worked less well.Conclusion
The trial team concluded that the addition of marizomib did not help prolong life or delay cancer growth.
The team found that with the addition of marizomib to standard treatment, side effects were worse.
The team found that with the addition of marizomib to standard treatment, the quality of life of people was worse than without marizomib.
All trial results help doctors and researchers understand more about different cancers and the best way to treat them.REC name
London - Central Research Ethics Committee
REC reference
18/LO/1106
Date of REC Opinion
24 Aug 2018
REC opinion
Further Information Favourable Opinion