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

Cancer type:

All cancer types
Bladder cancer

Status:

Results

Phase:

Phase 1/2

This trial looked at adding a drug called guadecitabine to cisplatin and gemcitabine chemotherapy. It included people with any solid tumour. And part of the trial included people with bladder cancer who were due to have surgery. 

A solid tumour Open a glossary item in this trial was any cancer apart from leukaemia Open a glossary item. An advanced solid tumour is a cancer that has spread or continued to grow despite treatment. 

This trial was open for people to join between 2016 and 2019. The team published the results in 2021.

Cancer Research UK supports this trial.

More about this trial

Cancer cells often contain genes Open a glossary item that can be switched off. This allows the cancer to grow. This also causes some cancers to become resistant to treatment with chemotherapy.

Guadecitabine (SGI-110) belongs to a group of drugs called DNA methytransferase inhibitors. It stops the action of a protein called DNA methyltransferase and switches the genes back on. Researchers thought this might stop the cancer growing. And help chemotherapy to work better.
    
Gemcitabine and cisplatin are 2 chemotherapy drugs. They are often used together to treat different types of cancer, including bladder cancer
 
The trial had 2 parts:

  • part 1 was for people with any solid tumour
  • part 2 was for people with bladder cancer that had not spread to lymph nodes Open a glossary item or elsewhere in the body. They all had surgery planned with the aim of curing their cancer.

The main aims of this trial were to:

  • find the best dose of guadecitabine in combination with chemotherapy 
  • learn more about the side effects of having these treatments together
  • see what happens to guadecitabine in the body
  • find out whether guadecitabine and chemotherapy before surgery improves treatment 

Summary of results

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 Open a glossary item They had:

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

They had between 3 and 4 cycles of treatment. 

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 Open a glossary item. This can cause an increased risk of infection.
  • a drop in the number of platelets Open a glossary item. 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 Open a glossary item)
  • how the drug worked and the effect it has on the body (pharmacodynamics Open a glossary item)

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 Open a glossary item) 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.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Simon Crabb

Supported by

Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
Southampton University Hospitals NHS Trust

Other information

This is Cancer Research UK trial number CRUKD/16/004.

Freephone 0808 800 4040

Last review date

CRUK internal database number:

13893

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Around 1 in 5 people take part in clinical trials

3 phases of trials

Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.

Last reviewed:

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