VINILO
Research type
Research Study
Full title
PHASE I-II STUDY OF VINBLASTINE IN COMBINATION WITH NILOTINIB IN CHILDREN, ADOLESCENTS AND YOUNG ADULTS WITH REFRACTORY OR RECURRENT LOW-GRADE GLIOMA
IRAS ID
130824
Contact name
Susan Picton
Contact email
Sponsor organisation
Gustave Roussy
Eudract number
2012-003005-10
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 5 months, 30 days
Research summary
Summary of research
Low grade gliomas (LGG) are the most frequent brain tumour in children. More than 50% of these tumours will progress within the first 5 years and need further treatment. As most patients are young, the risks of radiotherapy to the developing brain are high, further medical treatment options are urgently needed.
Vinblastine is an effective chemotherapy drug for LGG and has been shown to improve survival.
Nilotinib is type of biological therapy called a tyrosine kinase inhibitor.
Vinblastine and Nilotinib have different antiangiogenic mechanisms, limited and non-overlapping toxicities, and are thought to play an interesting role in the treatment of paediatric LGG.
The phase I part of the trial has already been completed and identified the recommended doses (RD) of each agent when given in combination.
The main objective of the phase II part is to evaluate the efficacy of vinblastine in combination with nilotinib at the RD, as compared to vinblastine alone, in children, adolescents, and young adults with refractory or recurrent LGG.
This is an open label, randomised, study of the combination of nilotinib and vinblastine versus vinblastine alone
122 patients with LGG will be randomised to receive either:
• Vinblastine and nilotinib OR
• Vinblastine only
Vinblastine will be given as an intravenous injection on days 1, 8, 15 and 22 of each 28 day cycle. Nilotinib will be taken as a capsule orally twice a day on each day of the cycle. Patients will receive up to 12 cycles of treatment in the trial as long as they are benefitting from it and are well.This trial is being funded in the UK by Cancer Research UK (including funding from the Brain Tumour Charity). Nilotinib is being provided free of charge by Novartis.
This trial will open at 6 sites in the UK plus others within Europe.
The Sponsor of this international study is Gustave Roussy, France.Summary of results
Abstract:
Purpose of the study: To see whether combining the drug nilotinib with vinblastine is better than using vinblastine alone in the treatment of low grade glioma (LGG).What was tested: Vinblastine alone was compared to vinblastine plus nilotinib in a phase 2 trial. In a phase 2 study, a comparison can be made with a smaller number of patients to see if it’s worthwhile doing a larger trial.
People taking part: 109 children, adolescents and young adults with low grade glioma from across Europe took part and were recruited over approximately 3 years. 23 patients were recruited in the United Kingdom
Results: The combination of vinblastine plus nilotinib was less effective than vinblastine alone in terms of the length of time to disease progression.
Safety: In this study, researchers found that the level of side effects was lower for the vinblastine plus nilotinib treatment group.
Who sponsored this study?
This study was sponsored by Gustave Roussy, France. The Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham was the co-ordinating clinical trials unit in the UK. The VINILO trials office can be contacted via VINILO@trials.bham.ac.uk.General Information about the trial
The study took place in France, United Kingdom, Italy, The Netherlands, Austria, Germany, Spain, Switzerland and Denmark. Recruitment began in the UK in February 2012 and ended in May 2019 when a planned statistical analysis of the results showed that patients receiving vinblastine alone had a longer time to disease progression than patients on vinblastine plus nilotinib. The trial closed in September 2021.The main objective of the study was to test if the combination of vinblastine and nilotinib was better than vinblastine alone in terms of progression free survival for:
• Children, adolescents and young adults with LGG that had not responded to treatment or which had returned after treatment
and
• Children, adolescents and young adults newly diagnosed with LGG who had the brain tumour predisposition syndrome neurofibromatosis 1 (NF1).Vinblastine alone is already used to treat patients with LGG and by giving nilotinib as well, patients could receive a lower dose of vinblastine so that there would be fewer side effects. Nilotinib is already used to treat adults with a certain type of leukaemia and is known to be generally well tolerated in children. Nilotinib had already been given in combination with the vinblastine to 35 children with LGG (as part a clinical trial) and the side effects were found to be manageable.
What patients were included in this study?
This trial included patients with LGG which was refractory (previous treatment had not worked) or recurrent (their cancer had returned after previous treatment) and patients with LGG at diagnosis who have the brain tumour predisposition syndrome NF1 and who had not received any previous treatment.
The trial was open to all children and young adults aged between 6 months and 21 years old.Patients needed to have adequate liver, heart and kidney function to participate and to have a life expectancy of more than 3 months. The patient or their parent or legal representative had to give informed consent to participate in the trial.
Patients were not able to participate in the trial if they had not recovered from the side effects of previous treatment, had significant heart or gastrointestinal disease, had another severe condition or were being treated with anti-epileptic medication or other medication affecting the function of the heart. Patients also could not be receiving treatment with anti-tumour drugs or have active symptoms of a fungal, viral or bacterial infection. Patients who had reached puberty needed to agree to use effective contraception during the trial and female patients could not be pregnant or lactating at trial entry.
Which medicines were studied?
Patients were randomly allocated into equal groups to receive vinblastine alone or vinblastine plus nilotinib. Vinblastine is a chemotherapy drug used to treat many different cancers, including lymphomas, bladder, breast, testicular and others. It is often given as part of the standard treatment for LGG. It works by damaging a part of the tumour cell that stops the cell from separating into two new cells and so stops the growth of the tumour. Nilotinib is a type of drug called a tyrosine kinase inhibitor. It works by blocking signals within the tumour cells that make them grow. Blocking the signals causes the cells to die.
What were the side effects?
Serious Adverse Events (SAEs) were reported from the time that informed consent was given for the trial up to 30 days after trial treatment finished. SAEs include untoward medical occurrences that result in patients being admitted to hospital, are life threatening, result in death, cause long term or significant disability or incapacity or cause birth defects.
240 SAEs were reported of which 144 occurred in patients on the vinblastine alone treatment and 96 occurred in patients on the vinblastine plus nilotinib treatment.
What were the overall results of the study?
It was concluded that the combination of vinblastine and nilotinib was not better than vinblastine alone for patients with LGG.
The research team looked at the time it took for disease progression to occur in patients on the trial. This was worse for the vinblastine plus nilotinib group than the vinblastine alone group (28% of patients in the vinblastine plus nilotinib group had not progressed after 2 years compared to 49% of patients in the vinblastine alone group).
The research team concluded that vinblastine plus nilotinib is a less effective treatment for patients with LGG than vinblastine alone. This may be because the dose of vinblastine was lowered for those patients also receiving nilotinib.
How has this study helped patients and researchers?
The study has shown that treatment with a combination of a lower dose of vinblastine plus nilotinib is not as effective for children adolescents and young adults with LGG as treatment with the usual dose of vinblastine.
It is important to note that this outcome reflects this specific trial and other trials may show something different.Are there plans for further studies?
NoWhere can I find more information about this study?
To learn about this study, you can find more detailed information on the EU database.REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
16/YH/0452
Date of REC Opinion
21 Nov 2016
REC opinion
Further Information Favourable Opinion