A trial looking at guadecitabine with cisplatin and gemcitabine for advanced solid tumours (SPIRE)

The trial team found the best dose and schedule of guadecitabine to have with chemotherapy. They also found the side effects of having this combination were manageable. They think this combination of treatment is promising. But it is too early to make firm conclusions about how well it works.

Trial design
This was a phase 1/2 trial. There were 2 parts to the trial. Part 1 was to find the best dose of guadecitabine to have in combination with chemotherapy. Part 2 tested this dose in people who had bladder cancer. 

Everyone had treatment in cycles. Each 21 day period was a cycle of treatment  They had:

• guadecitabine as an injection under the skin 
• cisplatin and gemcitabine through a drip into the bloodstream 

The schedule was as follows: 

• guadecitabine on day 1 to 5
• gemcitabine and cisplatin on day 8
• gemcitabine on day 15

Part 1
17 people joined part 1. They had up to 6 cycles of treatment.

The first few people taking part had a low dose of guadecitabine. The next few people had a higher dose if they didn’t have any side effects. And so on, until the researchers found the best dose to give. This is called a dose escalation study. 

Results for part 1 
The trial team found the best dose of guadecitabine to give in part 1. They used this dose for people who joined part 2 of the trial. 

Part 2
20 people joined part 2. They were put into a treatment group at random:

• 10 had gemcitabine and cisplatin
• 10 had gemcitabine, cisplatin and guadecitabine

Diagram 1

Results for part 2
The team looked at who went on to have their bladder cancer surgery as planned. This was:

• 8 people who had gemcitabine and cisplatin
• 8 people who had gemcitabine, cisplatin and guadecitabine

2 people didn’t have surgery and had chemoradiotherapy. The team found that adding guadecitabine didn’t cause a delay in further planned treatment. 

The team also looked at whose cancer had gone away completely. There were no signs of cancer at surgery in:

• 4 people who had gemcitabine and chemotherapy 
• 2 people who had guadecitabine, gemcitabine and cisplatin 

Side effects 
The side effects in both parts of the trial were similar. 

The team looked at the number of people who had bad to severe side effects. They found the most common was a:

• a drop in the number neutrophils . This can cause an increased risk of infection.
• a drop in the number of platelets . This can cause an increased risk of bleeding.

To help with the increased risk of infection everyone had injections with G-CSF. It is a type of growth factor that makes the bone marrow produce more white blood cells. This can reduce the risk of infection. 

Most people had their treatment delayed or reduced at some point during the trial. 7 people stopped treatment early due to side effects in part 1. 

1 person in each group stopped treatment early due to side effects in part 2. 

Blood samples for research 
The team collected blood samples. They looked at:

• what happened to guadecitabine in the body (pharmacokinetics )
• how the drug worked and the effect it has on the body (pharmacodynamics )

The team found guadecitabine was targeting the gene at the correct timepoint. This means it was working as planned and switching the genes back on. 

Conclusion
The team found the best dose and schedule of guadecitabine to give. This was the dose they recommended having with cisplatin and gemcitabine. Having guadecitabine caused a few more side effects but adding G-CSF helped.

The team also found that adding guadecitabine didn’t delay further treatment. 

The team say this combination of treatment is promising. But it is too early to make firm conclusions about how well it works. Researchers need to do more trials to investigate this. The trial team are planning another trial to do this. 

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.