A trial looking at SGI-110 with cisplatin and gemcitabine for advanced solid tumours (SPIRE)

Cancer type:

All cancer types
Bladder cancer

Status:

Open

Phase:

Phase 1/2

This trial is for people with advanced solid tumour and people with bladder cancer who are due to have surgery to remove their bladder. 

Solid tumours in this trial are any cancer apart from a leukaemia Open a glossary item. An advanced solid tumour is a cancer that has grown into surrounding tissue (locally advanced) or spread to another part of your body (advanced). 

Cancer Research UK supports this trial.

More about this trial

Cancer cells often contain genes that can be switched off, allowing the cancer to grow. This also causes some cancers to become resistant to treatment with chemotherapy.

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 think this might stop the cancer growing and make it more sensitive to chemotherapy.
    
Gemcitabine and cisplatin are 2 chemotherapy drugs. They are often used together to treat different types of cancer, including bladder cancer
 
This trial has 2 parts. The first part is for people with advanced solid tumours. The second part is for people with bladder cancer who are due to have surgery with the aim of curing their disease.

The aims of this trial are to  

  • find the best dose of SGI-110 in combination with chemotherapy 
  • learn more about the side effects of having these treatments together
  • see what happens to SGI-110 in the body
  • find out whether SGI-110 and chemotherapy before surgery works better than chemotherapy alone for bladder cancer

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you. 

You may be able to join the first part of the trial if 

  • You have a solid tumour that has grown into surrounding tissue (locally advanced) or spread to another part of your body (advanced). In this trial, a solid tumour means that you have any type of cancer apart from leukaemia 
  • The doctor running this trial thinks that chemotherapy with gemcitabine and cisplatin is an appropriate treatment for you. You can already have had chemotherapy 

You may be able to join the second part of the trial if you 

As well as the above, all the following must apply. You

  • Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1
  • Have satisfactory blood test results
  • Are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance that you or your partner could become pregnant
  • Are at least 16 years old

You cannot join this trial if any of these apply. 

  • You have cancer that has spread to your brain or spinal cord (central nervous system) and this hasn’t been treated or is causing symptoms. You can take part if the cancer spread to your brain has been treated, is not getting worse and you have not needed to take steroids in the last 4 weeks 
  • You have had major surgery in the last 30 days
  • You have had treatment with radiotherapy to more than 30% of your bone marrow Open a glossary item
  • You are still having side effects from any anti cancer treatment, apart from hair loss
  • Your kidneys are not working well enough to have treatment in this trial, you have tests to check for this
  • Have heart problems, such as a heart attack or angina that is difficult to control, in the last 6 months
  • You are allergic to the drugs used in this trial
  • You have had a live vaccine in the last 30 days
  • You are pregnant or breast feeding

If you are in part 2, you cannot join if you have had any other cancer in the last 2 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated 

Trial design

This is a phase 1/2 trial. There are 2 parts to this trial.

Part 1
The researchers need up to 30 people to join part 1. Everyone has SGI-110 and cisplatin and gemcitabine. 

The first few people joining have a low dose of SGI-110. If they don’t have any serious side effects, the next few people have a higher dose. And so on, until the trial doctors find the best dose. This is called a dose escalation study. 

People in this part of the trial have different types of cancer, this might include people with bladder cancer. 

When the best dose is found, 6 people with advanced bladder cancer have chemotherapy and SGI-110. This is so that the trial doctors can collect further information about the side effects to make sure that the trial can move to part 2.

The first day of treatment is called day 1. You have SGI-110 as an injection into the layer of fat just under the skin (subcutaneous injection). A doctor or nurse gives you the injection, usually into your tummy area. 

You have the injection slowly, it might take up to a minute. You have an injection of SGI-110 every day for 5 days. 

You have cisplatin on day 8. You have this and extra fluids through a drip into a vein. This takes about 4 hours.

You have gemcitabine on days 8 and 15. You have this through a drip into a vein and it takes between 30 to 60 minutes. 

Some people might need to have the drug G-CSF. G-CSF helps the body to make white blood cells to reduce the risk of infection. You have this as an injection just under the skin on days 15 to 21. 

Each 21day period is called a cycle of treatment. You have up to 6 cycles of treatment

Part 2  
The researchers need about 20 people with bladder cancer to join part 2. 

This part is randomised, the people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.  

  • one group have chemotherapy and SGI-110
  • the other group has chemotherapy – this is standard treatment 

Diagram showing SPIRE randomisation

Everybody has the best dose of SGI-110 found in the first part. You have SGI-110 and the chemotherapy drugs in the same way as described in part 1. 

You have 3 or 4 cycles of treatment. 

You then have surgery to remove your bladder as planned.

Both groups
You have extra blood samples as a result of taking part in this trial 

  • at the beginning of the trial
  • twice during each cycle of treatment
  • at the end of the trial

Where possible you have these at the same time as your routine blood tests.

The researchers also want to look at any previous and future samples of your cancer removed as part of a routine biopsy Open a glossary item or surgery. You do not have any biopsies as a result of taking part in this trial. 

The researchers use these blood and cancer samples to find out what happens to SGI-110 in the body (pharmacokinetics Open a glossary item) and how it might work with chemotherapy to treat cancer.

Hospital visits

You see the doctors and have some tests before you start treatment. The tests include 

  • Blood tests
  • Urine test
  • Physical examination

You go to hospital to have 

  • SGI-110 every day for the first 5 days 
  • Cisplatin and gemcitabine on day 8
  • Gemcitabine on day 15 

You see a doctor who will ask you if you have any side effects and you have further blood tests. 

If you have any scans as part of your routine care, the trial team will collect information about the results. 

You see the trial doctor about 1 month after you have finished treatment in this trial. You continue to see them every 2 or 3 months until your side effects are quite mild or have stopped. 

Side effects

As SGI-110 is quite a new drug, there may be some side effects we don’t know about yet. The trial team will monitor you during the time you have treatment and you will be given a phone number to call them if you are worried about anything.

Possible side effects include

The most common side effects of cisplatin and gemcitabine include

  • a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness 
  • tiredness (fatigue)
  • feeling or being sick
  • loss of appetite
  • hair loss 
  • numbness and tingling in your hands and feet (peripheral neuropathy)

We have more information about cisplatin and gemcitabine (GC).

Location

Sheffield
Southampton
Sutton

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

Questions about cancer? Contact our information nurses

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.

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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