A trial of AZD3965 for advanced cancer

The research team found the best dose of AZD3965 to give. And found out more about the side effects. 

Trial design
This trial was for people whose cancer had continued to grow despite treatment. There were no other standard treatments available for them to have.

This was a phase 1 trial. Everyone taking part took AZD3965 capsules. People in different groups had different doses. Some groups had treatment once a day, others had treatment twice a day.

This trial was done in 2 parts.

Part 1 was a dose escalation. It was for people with a solid tumour  or lymphoma. The first few people had the lowest dose of AZD3965. As they didn’t have any serious side effects, the next few people had a higher dose. And so on, until they found the best dose to give.

Part 2 was for people with types of non-Hodgkin lymphoma called Burkitt lymphoma or diffuse large B cell lymphoma. Everyone in this part had the same dose of AZD3965. The research team chose the best dose to give based on the results of part 1.

Results
A total of 51 people had treatment as part of this trial. There were:

• 40 people in part 1
• 11 people in part 2

Diagram of trial groups

The people in part 1 had a number of different cancers including bowel cancer and mesothelioma. The people in part 2 all had diffuse large B cell lymphoma (DLBCL).

Side effects
Many people taking part had at least 1 side effect caused by AZD3965. Some side effects were mild or didn’t last long. But some side effects were more serious. 

Researchers can class a side effect as serious for a number of reasons, including if:

• the person has to go to hospital because of it
• it is particularly important for the trial or the treatment being looked at

Side effects in part 1
In total, out of 40 people:

• 29 people (73%) had at least 1 side effect
• 5 people (13%) had at least 1 serious side effect

The most common side effects were:

• temporary changes to the back of the eye (retina) 
• extreme tiredness (fatigue)

The most common serious side effect was a temporary change to the back of the eye. Two people had this side effect.

There were 4 other serious side effects in part 1:

• 1 person had a condition where blood cells are not made properly (myelodysplastic syndrome or MDS)
• 1 person had lung inflammation (pneumonitis)
• 1 person was sick (vomiting) and had too much acid in the body (metabolic acidosis)

People treated at the highest dose in part 1 had too many major side effects. So the team decided it was best to use the dose below the highest dose for part 2.

Side effects in part 2
In total, out of 11 people:

• 9 people (82%) had at least 1 side effect
• 4 people (36%) had at least 1 serious side effect

The most common side effect in part 2 was extreme tiredness (fatigue). Three people had this side effect.

There were 7 serious side effects in part 2:

• 1 person had an increased level of a protein called troponin, which can indicate heart damage
• 1 person had a lung infection and an increased level of calcium in the blood
• 1 person had headaches and was sick (vomiting)
• 1 person had a severe general infection of the body (sepsis) and problems going for a wee (urinary retention)

What happened to AZD3965 in the body
The research team measured how much AZD3965 was in blood samples at various points after people took the capsules. 

They discovered the level stayed more stable if people had smaller doses of AZD3965, more often. So they recommended that people have their treatment split into 2 doses each day.

How well treatment worked
The research team looked at blood samples to see if AZD3965 made cancer cells die. They weren’t able to draw any conclusions about this because there were problems getting useful results from the tests.

The research team also looked at scans to see how well AZD3965 worked at making cancer go away for people in part 2.  It’s hard to draw any firm conclusions about this because:

• there was a small number of people in the trial
• some people didn’t have treatment for very long

They were able to assess this in 3 people in part 2. They found that the lymphoma:

• went away in 1 person
• stayed the same in 1 person
• continued to grow in 1 person

The person whose cancer went away continued to take AZD3965 for 16 months before their lymphoma started to grow again.

Conclusion
The research team found the highest dose of AZD3965 that is safe to use. They also learnt about the side effects and what happens to AZD3965 in the body. These results will help researchers learn more about cancer and how to treat it. 

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.