A trial looking at low dose cyclophosphamide and nintedanib for ovarian cancer (METRO-BIBF)

The team found that adding nintedanib to cyclophosphamide didn't work. It didn't improve treatment for ovarian cancer that had come back.

Trial design
This was a phase 2 trial. There were 2 treatment groups. 117 people took part. They were put into a treatment group at random:

• 59 had low dose cyclophosphamide and nintedanib
• 58 had low dose cyclophosphamide and a dummy drug 

Diagram 1

Results
The team looked at the median overall survival. This is the time from treatment to the point at which half of the patients are living. 

It was: 

• 6.8 months in people who had cyclophosphamide and nintedanib
• 6.4 months in people who had cyclophosphamide and a dummy drug

The team also looked at how long people lived before their cancer started to grow again. At 6 months the team found little difference between the 2 different groups. It was: 

• 2.9 months in people who had cyclophosphamide and nintedanib
• 2.6 months in people who had cyclophosphamide and a dummy drug

Other findings included:

• people who had a drug called bevacizumab in the past stopped treatment earlier. They had about 52 days less time on treatment.
• more people than expected had treatment for at least 6 months

Quality of life
The team looked at how treatment affected quality of life. They didn’t find a difference between the 2 treatment groups. 

Side effects
The team looked at the number of people in each group who had bad to severe side effects. They found it was:

• just over 6 out of 10 (64%) people who had cyclophosphamide and nintedanib
• just over 5 out of 10 (54%) people who had cyclophosphamide and a dummy drug

The most common side effects were: 

• a drop in the number of white blood cells called lymphocytes 
• tiredness (fatigue)
• being sick 

People who had nintedanib also had bad to severe:

• risk of infection (neutropenia)
• diarrhoea 

People who had  low dose cyclophosphamide and the dummy drug  had more problems with tummy pain. 

There were a lot of side effects in the first 6 weeks of treatment. It was difficult to work out if:

• nintedanib was causing them
• they were symptoms that cancer can cause 

The data monitoring committee looked at the side effects. This committee monitors the safety and design of trials. They looked at the number of side effects and how bad they were. They did this after 61 people had joined the trial. 

The committee recommended the team reduce the dose of nintedanib. People who joined the trial after this point had the lower dose. 

Conclusion
The research team concluded that adding nintedanib to cyclophosphamide didn’t work. It didn't increase the length of time people lived. 

There was some evidence that low dose cyclophosphamide helped a few people. The trial team suggest it might be a suitable treatment option for some people. 

Even so, all trial results help doctors and researchers understand more about different cancers. And the best way to treat them. 

Where this information comes from    
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.