A trial of vandetanib and selumetinib for solid tumours including non small cell lung cancer (VanSel-1)

The research team found that having vandetanib and selumetinib at the same time didn’t cause too many side effects. And that taking vandetanib with selumetinib didn’t seem to affect the level of each drug in the body.

Trial design
There were two parts to this phase 1 trial.

Part one was dose escalation. The first few people had the lowest dose of treatment. As they didn’t have any major side effects, the next few people had a higher dose. And so on, until they found the best dose to give. 

This part was for people with any solid tumour. Most people taking part had bowel cancer or lung cancer.

Part two was dose expansion. Everyone in this part of the trial had the same dose of treatment. The research team used the results from part one to decide what dose to give. The people in this part all had non small cell lung cancer.

Results
A total of 58 people had treatment as part of this trial. 

• 47 in part one (dose escalation)
• 11 in part two (dose expansion)

One person had vandetanib, but didn’t have selumetinib. The other 57 people had both vandetanib and selumetinib.

VanSel trial results - randomisation diagram

There were 7 groups in the dose escalation part of the trial. There were 6 to 8 people in each group. People who had the highest dose in part one had too many major side effects. So the team decided it was best to use the dose below the highest dose for part two.

Side effects
Everyone taking part had at least one non serious side effect. These are often mild or don’t last long.

The most common non serious side effects were:

• 44 people (76%) had diarrhoea
• 24 people (41%) had a rash
• 20 people (34%) had extreme tiredness (fatigue)
• 19 people (33%) felt sick (nausea)
• 15 people (26%) were sick (vomited)

VanSel trial results - bar chart showing the most common non serious side effects

Serious side effects
Researchers class a side effect as serious for a number of reasons, including when:

• the person has to go to hospital because of it
• it is particularly important for the specific treatment in the trial

In this trial, 42 out of 57 people (74%) had at least one side effect that was classed as serious.

The most common serious side effects are listed below.

• 12 people (21%) had problems with the retina in the eye
• 11 people (19%) had diarrhoea
• 9 people (16%) had a rash

These and the other serious side effects are shown here:

VanSel trial results - bar chart

Finding the best dose to use
Nine people had a side effect that was significant enough to suggest the dose they were having was too high. The trial team used this information to decide which dose to use.

These side effects were:

• increased blood pressure
• slow heart rate (pulse)
• abnormal heart rhythm
• problems with the retina in the eye 
• sore mouth (mucositis)
• increased level of a protein called alkaline phosphatase 

About 3 out of 10 people (30%) stopped treatment because of side effects they were having.

What happened to vandetanib and selumetinib in the body
The research team measured the amount of vandetanib and selumetinib in blood samples at various points after treatment. 

They found that taking vandetanib with selumetinib did not affect the level of either of the drugs in the body.

How well treatment worked
It’s hard to draw any firm conclusions about this because of the small number of people in the trial. And because people in different groups had different doses of treatment.

The trial team were able to assess how well treatment worked in 39 people in part one. The cancer:

• stayed the same for 15 people (38%)
• continued to grow for 24 people (62%)

One person whose cancer stayed the same continued on treatment for 5 years and 9 months before their cancer symptoms got worse.

The trial team looked at how well treatment worked for 9 people in part two. The cancer:

• stayed the same for 4 people (44%)
• continued to grow for 3 people (33%)

They were not able to measure this for 2 people (22%)

Two patients in part two (22%) were living one year after starting treatment. 

Conclusion
The research team found a dose of the combination of vandetanib and selumetinib that didn’t cause too many side effects. It’s hard to say for sure how well it works as a treatment for cancer. 

Taking vandetanib with selumetinib did not seem to have an effect on the level of each of the drugs in the body.

Other trials in the future may show different results.

Future plans
At the time of writing this summary there were no other trials planned for the combination of vandetanib and selumetinib.

Where this information comes from
We have based this summary on information from the research team. As far as we are aware, the information they sent us has not been reviewed independently (peer reviewed ) or published in a medical journal yet. The figures we quote above were provided by the research team. We have not analysed the data ourselves.