A trial looking at LY3143921 hydrate for advanced cancer

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

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:

Closed

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:

bowel (colorectal) cancer
a type of ovarian cancer called serous ovarian cancer that is fast growing (high grade)
non small cell lung cancer
cancer of the oesophagus (foodpipe)
head and neck cancer
cancers of the urinary tract (urothelial cancer), such as bladder cancer
breast cancer that does not have receptors for the hormones oestrogen and progesterone or the HER2 protein (triple negative breast cancer)
pancreatic cancer

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 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 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. The researchers expect to recruit between 68 to 80 people. This trial has 2 parts.

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 once a day, or twice a day. Whether you have capsules once or twice a day depends on when you join the trial.

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 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 or times each day. Swallow your tablets whole with water.

On certain days, you may be asked to take the capsules on an empty stomach. So you don’t eat anything 3 hours before and 2 hours after you take the capsules (you can still drink water). Your doctor or nurse will tell you if you need to take your capsules on an empty stomach and when.

Part 2
You have the best dose and frequency of LY3143921 hydrate found in part 1. So this might be once or twice a day, depending on what was decided as a result of part 1.

You take LY3143921 hydrate capsules as described in part 1, except you do not have a single dose for your first treatment.

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 )
heart scan (echocardiogram or MUGA 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

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
3 to 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.