A study looking at cediranib and selumetinib with chemotherapy and radiotherapy for rectal cancer (DREAMtherapy)

The research team found that cediranib may be a useful treatment for rectal cancer, but that selumetinib caused too many side effects.

Trial design
The research team ran this as a dual study, looking at two treatments at the same time. It was also what’s called a phase 1 dose escalation study.

The first few people who took part had the lowest dose of cediranib. When they finished treatment, the next few people taking part had selumetinib. And when they finished treatment, the next few people had cediranib again, but at a higher dose. And so on, until they found the best dose of each treatment to give without causing too many side effects.

A total of 30 people joined the study:

• 18 people had cediranib
• 12 people had selumetinib

Diagram 1

Cediranib results
A total of 18 people had cediranib as part of this trial, in 3 groups. Each group had a different dose.

People who had the highest dose had more severe side effects including diarrhoea and extreme tiredness (fatigue). So the research team concluded that the middle dose was the best dose to use.

The research team looked at how well the treatment worked for 17 of the people who took part. They found that the cancer got smaller in 9 of them (53%). This is higher than expected with standard chemoradiotherapy.

The researchers measured the amount of different proteins in blood samples from those who took part. They found that treatment tended to work better for people with less of a protein called tumour necrosis factor (TNF).

Selumetinib results
A total of 12 people had selumetinib as part of this trial, in 2 groups:

• 8 people in the first group had a lower dose, twice a day
• 4 people in the second group had a higher dose, once a day

Some people in both groups had severe side effects such as diarrhoea. And this meant some people needed to have a lower dose of either chemotherapy or radiotherapy than normal. So the research team decided not to continue looking at selumetinib as part of this trial.

When the research team looked at how well the treatment had worked, they found the cancer had got smaller in 2 out of 12 people (17%).

Conclusion
The trial team concluded that:

• it is possible to run a dual trial in this way
• cediranib didn’t cause too many side effects and could be a useful treatment for people with locally advanced rectal cancer
• the level of tumour necrosis factor (TNF) may help predict who will benefit most from treatment 
• selumetinib caused too many side effects to be a treatment for this group of patients

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.