A trial of MK-8242 for advanced solid tumours

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

Cancer type:

All cancer types

Status:

Closed

Phase:

Phase 1

This trial is looking at a drug called MK-8242 for people who have a solid tumour for which there is no other treatment available. A solid tumour Open a glossary item is any type of cancer other than leukaemia or lymphoma .

Some genes help to stop cancer cells growing. They are called tumour suppressor genes. P53 Open a glossary item is an important tumour suppressor gene.

A protein called HDM2 stops p53 working. The drug being looked at in this trial blocks HDM2. This allows p53 to work and stops the growth of cancer cells. The drug is called MK-8242.

In some cancers, the p53 gene is abnormal. But in order for MK-8242 to work, it is important that the p53 gene in the cancer cells is normal. The first few people joining this trial will not have their cancer’s p53 gene tested. But people joining the trial later can only take part if tests show that their tumour has a normal p53 gene. Researchers can check this by looking at a sample of the tumour.

The aims of the trial are to

Find the highest dose of MK-8242 you can safely have
Learn more about how the drug works and what happens to it in your body
See what effect MK-8242 has on solid tumours with a normal p53 gene

Who can enter

You may be able to join this trial if all of the following apply. You

Have a solid tumour that is advanced and for which there is no other standard treatment available
Have at least one area of cancer that has not been treated with radiotherapy and can be seen and measured on a scan
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 at least 18 years old
Agree to use 2 forms of reliable contraception during the trial and for 2 months afterwards if there is any chance you or your partner could become pregnant

Apart from the first few people joining the trial, you must give permission for the trial team to get a sample of your tumour and tests must show that the cancer cells have a normal p53 gene.

If you have prostate cancer, and have not had an operation to remove your testicles (an orchidectomy), you must continue to have hormone injections to lower the amount of testosterone Open a glossary item in your body.

You cannot enter this trial if you

Have cancer that has spread to your brain or spinal cord (your central nervous system)
Have had chemotherapy or another experimental drug in the last 4 weeks
Have had radiotherapy in the last 2 weeks
Have started taking drugs called bisphosphonates in the last month, or have changed the dose in that time if you’ve been taking them for longer
Have not recovered from the side effects of other treatment unless they are very mild (apart from hair loss)
Are known to be very sensitive to MK-8242 or anything in it
Have had a heart attack in the last year or have certain other heart problems – the trial team can advise you about this
Have an infection that needs treating or any other medical condition that the trial doctors think could affect you taking part
Are hepatitis B, hepatitis C or HIV positive
Have taken medication that affects substances called cytochrome P (CYP) enzymes in the last week – your doctor can advise you about this
Are pregnant or breastfeeding

Trial design

This is a phase 1 trial. It will recruit 136 people. Everybody taking part will have MK-8242 in capsules that you swallow.

There are 2 parts to the trial. In the 1st part, the researchers are looking for the highest safe dose of MK-8242. The 2nd part is to learn more about the side effects and how tumours with a normal p53 gene respond to the drug.

The first few patients taking part will have low doses of the trial drug. If they don’t have any serious side effects, the next few patients will have a higher dose. And so on, until they find the best dose of MK-8242 to give. This is called a dose escalation study.

Everybody joining the 2nd part of the trial has the highest safe dose found in part 1.

You take MK-8242 every day for a week, followed by 2 weeks without any treatment. Each 3 week period is called a cycle of treatment. The trial team will tell you exactly how and when to take the capsules. You keep a diary at home to note down when you take them.

As long as you don’t have bad side effects, you can carry on taking MK-8242 for as long as it helps you.

The trial team may ask you to have more biopsies Open a glossary item during treatment to see what effect the drug is having. You don’t have to have these biopsies if you don’t want to. You can still take part in the trial.

Hospital visits

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

Physical examination
Heart trace (ECG )
Blood tests
Urine tests
CT scan

If you have prostate cancer, you also have a bone scan and PSA tests.

You go to hospital 4 times in the first cycle of treatment. You may need to stay in hospital overnight on a couple of occasions if you live a long distance from the Hospital.

You go to hospital 3 times in both the 2nd and 3rd cycles of treatment. After that, you go twice in each treatment cycle.

You have blood tests at each hospital visit. You have a CT scan every 9 weeks. Men with prostate cancer also have a bone scan every 9 weeks.

When you finish treatment, you see the trial team again a month later.