A trial of nivolumab and ipilimumab for men with prostate cancer (NEPTUNES)

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

Cancer type:

Prostate cancer

Secondary cancers

Status:

Closed

Phase:

Phase 2

This trial is for men with prostate cancer that has spread to other parts of the body (metastatic).

It is for men who:

have had surgery to remove the testicles (orchidectomy) or are having treatment with hormone therapy
have certain changes in their genes or proteins on the surface of cancer cells

More about this trial

Prostate cancer needs the male sex hormone testosterone to grow. Testosterone is produced by the testicles. So, for advanced prostate cancer you might have:

surgery to remove the testicles (orchidectomy)
hormone therapy to reduce the level of testosterone in your body

But after some time, prostate cancer can start to grow again because the treatment has stopped working. This is called castration resistant prostate cancer.

You usually have chemotherapy for castration resistant prostate cancer. But doctors are looking for new ways to help men in this situation. In this trial, they are looking at 2 drugs called nivolumab and ipilimumab.

Nivolumab and ipilimumab are 2 types of immunotherapy. Both drugs seek out cancer cells by looking for proteins on the surface of the cancer cells and blocking them so that the immune system Open a glossary item recognises them and kills them.

This trial is in 2 parts. First, doctors test a sample of your cancer for:

certain changes in the genes
cells of your immune system
proteins on the surface of cancer cells

Doctors call this immunogenic signature test. You go to the 2nd part of this trial if doctors find certain gene changes and a difference in the amount of proteins in the cell (positive immunogenic signature) that may make you more responsive to immunotherapy treatment Open a glossary item . In the 2nd part of this trial, you have nivolumab and ipilimumab.

The main aim of this trial is to find out whether nivolumab and ipilimumab help men with castration resistant prostate cancer who have a positive immunogenic signature test.

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.

Who can take part
You may be able to join the 1st part of this trial if all of the following apply:

you have adenocarcinoma of the prostate (prostate cancer) that has spread to other parts of the body
you are willing to have a sample of tissue taken (biopsy ) if there isn’t a suitable sample available that doctors can use for the immunogenic signature test
you are at least 18 years old
you have had treatment, or are currently having treatment, with abiraterone, enzalutamide, docetaxel, cabazitaxel or radium 223
doctors think that you might be able to join the 2nd part of this trial

You may be able to join the 2nd part of this trial if all of the following also applies:

you have certain changes in the genes of the cancer cells and there are differences in the amount of proteins in the cancer cell (immunogenic signature test positive)
you have had surgery to remove the testicles (orchidectomy) or you are currently having hormone therapy
you have had a CT scan or MRI scan to confirm that your cancer has spread to other parts of the body
you have low levels of testosterone in your body (less than 1.73 nmol/L)
your cancer got worse (progressed) in the last 6 months (your doctor can tell you more about this)
you are willing to have a new sample of tissue taken if doctors think it is safe and you haven’t had a biopsy during the 1st part of this trial
you have satisfactory blood tests results
your liver and kidneys are working well
you are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)
you are willing to use reliable contraception during treatment and for 7 months afterwards if there is any possibility your partner could become pregnant

Who can’t take part
You cannot join the 1st part of this trial if any of these apply.

Cancer related
You:

have had another cancer in the past 2 years, apart from successfully treated non melanoma skin cancer
have had treatment with sipuleucel-T, nivolumab, ipilimumab or any other similar drug
have had radiotherapy in the past 2 weeks

Medical conditions
You:

have had an autoimmune disease , apart from vitiligo, psoriasis and problems with your thyroid (hyperthyroidism or hypothyroidism)
have lung problems such as pneumonitis , interstitial lung disease or pneumonia
have problems with your bowels and your doctor think that you are at risk of having a blockage (obstruction) in the bowel
have heart problems such as angina that isn’t controlled, an irregular heartbeat (arrhythmias) or you have had a heart attack in the last 3 months
have problems with your adrenal glands that isn’t controlled
have type 1 diabetes that isn’t controlled
have had an organ transplant or a stem cell transplant from a donor (allogeneic stem cell transplant)
have moderate or severe problems with your nerves and this is causing numbness or tingling in fingers and toes (peripheral neuropathy)
have hepatitis B or hepatitis C
have HIV
have any other serious medical or mental health problem that the trial doctor think could affect you taking part

As well as the above, you cannot join the 2nd part of this trial if any of these also apply. You:

have had an experimental drug in the past month
have had antibiotics in the last 2 weeks, unless it was to prevent an infection
have had flutamide or cyproterone in the last 4 weeks
have had bicalutamide or nilutamide in the last 6 weeks
have had a severe infection in the last month
have taken drugs to damp down your immune system (immunosuppressants ) in the last 2 weeks, unless it was a very small dose or an inhaler
have had a live vaccine in the past month

Trial design

This is a phase 2 trial. Researchers need around 175 men to join the 1st part of this trial. They think that about 35 men will then have a positive immunogenic signature and be able to join the 2nd part.

This trial is in 2 parts:

part 1 is the pre screening
part 2 is the main study

Part 1 (pre screening)
Everyone gives a sample of tissue (archival tumour sample) for the immunogenic signature test. You need to have a biopsy if there isn’t a suitable sample available. Doctors look for:

changes in the genes
cells of your immune system
proteins on the surface of cancer cells

It might take a number of weeks to get the results from the immunogenic test. Your doctor might suggest that you have other treatments during this time.

The trial doctor will tell you the results of the test when available. You then:

join the 2nd part of this trial if the immunogenic signature test shows that you have certain features in your genes and immune system (immunogenic signature positive)
stop the trial if the immunogenic signature test is negative (your doctor will tell you which other treatments you might have)

Part 2 (main study)
There are 2 groups. But the dose you have in each group is different. Group 1 is now closed. So if you join the study now you join group 2.

Everyone has 4 cycles of treatment with nivolumab and ipilimumab. Each cycle of treatment takes 3 weeks. You have both drugs as a drip into a vein on the 1st day of each cycle. It takes about 1 and a half hours each time you have it.

After 4 treatment cycles of nivolumab and ipilimumab, you have no treatment for 3 weeks in group 2. You then have nivolumab on its own every 4 weeks. This continues for up to a year.

Blood tests
You have extra blood tests as part of this trial. Researchers want to look at the effect nivolumab and ipilimumab has in your body.

You have the extra blood tests before the start of treatment and at set times during the trial.

Hospital visits

You see a doctor and have some tests before taking part in the 2nd part of this trial. These tests might include:

physical examination
blood tests
urine test
heart trace (ECG )
CT scan and MRI scan
bone scan

During treatment, you see the trial doctor each time you have nivolumab and ipilimumab. You have blood tests, a heart trace and a physical examination each time you see them.

You have a CT scan and bone scan every 9 weeks for about 6 months. You then have a CT scan or bone scan every 12 weeks.

You continue to have treatment for as long as it is working and the side effects aren’t too bad. It can be for up to a year.

When you finish treatment, you see the trial doctor after a month. You then see them:

every 3 months for 2 years from the date your treatment started
then every 6 months for up to 5 years from the date your treatment started

Side effects

The trial team monitor you during the time you have treatment with nivolumab and ipilimumab, and afterwards. You have a phone number to call them if you are worried about anything.

The team will tell you about all the possible side effects before you start treatment. The most common side effects of nivolumab and ipilimumab are: