A trial looking at LY3143921 hydrate for advanced cancer

Cancer type:

Bladder cancer
Bowel (colorectal) cancer
Breast cancer
Head and neck cancers
Kidney cancer
Lung cancer
Non small cell lung cancer
Oesophageal cancer
Ovarian cancer
Pancreatic cancer

Status:

Open

Phase:

Phase 1

This trial is for people with some types of advanced cancer. An advanced cancer Open a glossary item is cancer that has spread locally into surrounding tissues or elsewhere in the body.  

The people taking part must have a cancer where treatment is no longer working (refractory cancer), or there is no suitable treatment available, or they don’t want the treatment that has been offered. 

Cancer Research UK supports this trial.

More about this trial

LY3143921 hydrate has shown some promise in laboratory research and animal studies. It is a type of drug called a Cdc7 inhibitor. Cdc7 helps our cells to make more copies of itself (multiply) in an ordered way. Low levels of Cdc7 are usually found in normal cells, but there can be higher levels of Cdc7 in cancer cells. 

Researchers think that LY3143921 hydrate can block the action of Cdc7. This could stop the cancer cells from multiplying and cause them to die. As normal cells have lower levels of Cdc7, they might be less affected by the drug. So a person might have fewer side effects.

This trial is looking at particular cancers that are thought to have higher levels of Cdc7. There are two parts to this trial. The first part is for people with:

The second part is for people with 1 of 2 types of cancer. The 2 types of cancer will be decided by the team when the trial is ready to move into the part 2. 

The aims of this trial are to:

  • find the best dose of LY3143921 hydrate to treat advanced cancer 
  • learn more about the side effects 
  • see what happens to LY3143921 hydrate in your body
  • find out how the drug affects cancer cells in the body

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. 

Part 1
For part 1, you may be able to join this trial if you have one of the following types of cancer that has spread (advanced cancer):

  • bowel (colorectal) cancer
  • serous ovarian cancer that is fast growing (high grade) 
  • squamous cell NSCLC
  • squamous cell oesophageal cancer 
  • squamous cell cancer Open a glossary item of the head and neck 
  • triple negative breast cancer 
  • pancreatic cancer 
  • cancers of the urinary tract (urothelial cancer)  

Urothelial cancers include cancer of the centre of the kidney (renal pelvis), bladder cancer, cancer of the tube that takes urine from the kidney to the bladder (ureter) or cancer of the tube that drains urine from the bladder and out of the body (urethra).

Part 2
For part 2, you may be able to join this trial if you have 1 of 2 types of advanced cancer (to be confirmed by the trial team) and you are willing to have a sample (biopsy) taken of your cancer spread before treatment and again during your first cycle of treatment.

As well as the above, all the following must apply for people in part 1 and 2. 

  • You have a cancer has spread locally into surrounding tissues or elsewhere in the body (advanced cancer)  
  • There is no suitable treatment available for your cancer, your treatment has stopped working or you don’t want to have the treatment that has been offered to you
  • You have cancer that can be measured using scans, or by the doctor examining you (you might not be able to take part if you have had radiotherapy treatment to the only area of cancer spread that can be measured) 
  • You agree to the trial team looking at a stored sample of tissue of your cancer taken when you were first diagnosed
  • You agree to have an extra blood sample taken for the purposes of this research. You have this on the first day of your treatment 
  • You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1
  • You have satisfactory blood test results
  • You are willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance that you or your partner could become pregnant
  • You are at least 18 years old

You cannot join this trial if any of these apply. You

Cancer related 

  • Have cancer that has spread to your brain or is pressing on your spinal cord (spinal cord compression) and this is causing symptoms.  
  • Have had hormone therapy or immunotherapy in the last 4 weeks 
  • Have had radiotherapy treatment to a large area of your bones 
  • Have had chemotherapy in the last 4 weeks (or 6 weeks if you have had a nitrosurea Open a glossary item chemotherapy drug or mitomycin C)
  • Have had major surgery in the last 4 weeks
  • Have had an experimental cancer drug in the last 4 weeks before starting the study treatment (you might still be able to join if you are taking part in a trial that does not involve a treatment)
  • Are still having side effects from any anti cancer treatment, unless they are mild. This does not include hair loss

Medical conditions

  • Have problems with low blood pressure (hypotension) that is causing you symptoms, or cannot be controlled with medication
  • Have problems with high blood pressure (hypertension) that cannot be controlled with medication
  • Have another condition that is affecting your whole body (systemic), for example you have an infection that needs treatment or cannot be controlled with treatment
  • Are known to be HIV, hepatitis B or hepatitis C positive 
  • Have heart problems such as heart failure that needs treating, unstable angina or you have had a heart attack in the last 6 months
  • Have eye problems such as glaucoma or dry eye syndrome 
  • Have any other serious medical condition that the trial team think could affect you taking part

Other

  • Are pregnant or breastfeeding

Trial design

This is a phase 1 trial. This trial has 2 parts. The researchers need up to 18 people for part 1 and up to 50 people for part 2.

In the first part of the trial, the first few patients joining have a low dose of LY3143921 hydrate. If they don’t have any serious side effects, the next few patients have a higher dose. And so on, until the doctors find the best dose to give. This is called the dose escalation phase. 

In the second part of the trial everybody has the best dose for advanced cancer found in the first part of the trial. This is called the dose expansion phase.

Part 1
You take LY3143921 hydrate as capsules. You have your first dose as a single dose. About a week later you start taking LY3143921 hydrate capsules every day. 

When you have your first dose you stay in hospital for between 1 and 3 nights. During this time the trial team monitor you closely for any side effects. You have tests to check your general health. For example, you have your heart rate and temperature measured. You have your blood pressure checked regularly over the 24 hours following your first dose.

You also have frequent blood tests to see how quickly this drug appears in your body and how quickly your body gets rid of (excretes) the drug. You have a blood test:

  • 8 times over the first 24 hours
  • once a day on days 2 and 3 

You then start treatment with LY3143921 hydrate once a day, for 21 days. How many capsules you take each time depends on the dose you have. Each 3 week period is called a cycle of treatment. You have up to 12 cycles as part of this trial. You do not have a break between cycles.  So your treatment could take up to 9 months.

You should take LY3143921 hydrate at the same time each day. Swallow your tablets whole with water. You should take the capsules on an empty stomach. So don’t eat anything 3 hours before and 2 hours after you take the capsules. 

Part 2
You have the best dose of LY3143921 hydrate for advanced cancer found in part 1. You have LY3143921 hydrate capsules as described in part 1, except you do not have a single dose for your first treatment. You start taking LY3143921 hydrate once a day every day. 

You stay in hospital for between 1 and 3 nights for your first 1 to 3 doses of LY3143921 hydrate. The trial team monitor you closely and you have frequent blood tests, as described in the first dose for part 1.

You have up to 12 cycles of treatment, so your treatment could take up to 9 months.

Tumour samples
The trial team look at a sample (biopsy Open a glossary item) of your cancer taken when you were first diagnosed with cancer.

If you are in part 2, you also have biopsies taken of your cancer before treatment and again during your first cycle of treatment. The trial team want to find out how LY3143921 hydrate works and which cancers benefit the most from this drug.

These samples might also be stored and used in future research.

Blood samples
You have extra blood tests as part of this trial. Where possible you have these at the same time as your routine blood tests. The researchers want to find out what happens to LY3143921 hydrate in the body (pharmacokinetics Open a glossary item). 

They will also look at the certain genes (pieces of DNA) to find out why this drug might benefit some people, but not others. 

Hospital visits

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

  • blood tests
  • physical examination including an eye examination
  • heart trace (ECG Open a glossary item)
  • heart scan (echocardiogram Open a glossary item or MUGA Open a glossary item scan)
  • a CT scan 

You might also have an MRI scan. 

At regular points throughout the trial, a nurse measures your:

  • weight
  • temperature
  • heart rate
  • blood pressure Open a glossary item

During your first cycle of treatment you are asked to record your blood pressure when at home. You do this twice a day when lying down and then standing up. You take you blood pressure:

  • before your dose of LY314392 hydrate
  • 6 hours afterwards

You are shown how to do this with a blood pressure device which you take home. You also keep a written record of your blood pressure readings and when you take your capsules. 

You go to hospital every week during the first 8 cycles of LY3143921 hydrate. These visits might be reduced to every 3 weeks for the remaining 4 cycles. You have some of the above tests again including blood pressure, urine and blood tests. A doctor or nurse will ask about any side effects.

You have an ECG at the start of cycles 2 and 3. You only have further ECGs if your doctor thinks you need them. You have a CT scan and, or an MRI scan after every 2 cycles. 

You have a final hospital appointment as part of this trial about 4 weeks after finishing treatment. Some of the tests are repeated and you might have a scan. 

The trial team will then contact you or your GP by telephone about every 3 months. They will check how you are and ask about your cancer.

Side effects

As LY3143921 hydrate is a new drug, there may be side effects that the trial team don’t know about yet. Possible side effects include:

  • feeling dizzy or light headed due to low blood pressure
  • eye pain and, or eyesight changes due to abnormal growth of blood vessels in your eyes

You have your blood pressure measured each time you visit hospital. And you will also measure your blood pressure at home during the first cycle. You will have clear instructions about what to do if you have low blood pressure.

You are asked not to wear contact lenses while you are taking LY3143921 hydrate. The trial team will check the health of your eyes before and regularly during your treatment. 

Location

Belfast
Edinburgh
Glasgow
Newcastle upon Tyne

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

Professor Richard Wilson

Supported by

Cancer Research UK
Eli Lilly and Company Limited

Other information

This is Cancer Research UK trial number CRUKD/17/004.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14696

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

Wendy took part in a new trial studying the possible side effect of hearing loss

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"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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