A trial of nivolumab and ipilimumab for small cell lung cancer (STIMULI)

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

Cancer type:

Lung cancer

Small cell lung cancer

Status:

Closed

Phase:

Phase 2

This trial is looking at whether adding nivolumab and ipilimumab after chemoradiotherapy helps to stop small cell lung cancer coming back.

It is for people who are going to have treatment for the first time for limited stage small cell lung cancer (SCLC). Limited stage SCLC is when the cancer is in a single area that can be treated with radiotherapy. It:

is only in one lung
may be in nearby lymph nodes

It is for people who are going to have treatment with chemotherapy and radiotherapy (chemoradiotherapy).

More about this trial

Chemoradiotherapy is a treatment for limited stage SCLC. You usually have radiotherapy to the lung and the chemotherapy drugs:

etoposide
cisplatin or carboplatin

After chemoradiotherapy, you usually have radiotherapy to the brain. This is to reduce the risk of cancer spreading there. This is called prophylactic cranial irradiation (PCI).

This is the standard treatment Open a glossary item

. After you finish treatment, your doctor monitors you regularly to look for signs of the cancer coming back. This is part of the normal follow up.

Sometimes SCLC comes back or continues to grow despite having standard treatment. In this trial, doctors are looking at the drugs nivolumab and ipilimumab to try to stop SCLC from coming back after chemoradiotherapy.

Nivolumab (Opdivo) and ipilimumab (Yervoy) are 2 types of cancer drugs called monoclonal antibodies. They work in slightly different ways but both help the body’s immune system to kill cancer cells.

This trial is in 2 parts. In the 1st part, everyone has the standard treatment, which is chemoradiotherapy. In the 2nd part, people have 1 of the following:

nivolumab and ipilimumab (experimental arm)
no more treatment (observation arm)

The main aim of this trial is to find out if having nivolumab and ipilimumab after the standard treatment helps to stop SCLC from coming back.

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 the trial if all of the following apply. You:

have limited stage small cell lung cancer (SCLC) (stage 1 to 3B)
are going to have treatment for limited stage SCLC for the 1st time
have at least 1 area of cancer that can be seen and measured on a scan
are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)
have satisfactory blood tests results
have satisfactory breathing test (pulmonary function) results
are at least 18 years old
are willing to use reliable contraception during treatment and for at least 12 months afterwards if there is any possibility you or your partner could become pregnant

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

you have finished the standard treatment (4 treatment cycles of chemoradiotherapy and PCI)
your cancer stayed the same or got better after the standard treatment
you have recovered from all moderate and severe side effects, apart from tiredness (fatigue), hair loss, loss of appetite, kidney problems and inflammation of the food pipe (oesophagitis)
you are up and about for more than half the day (performance status 0, 1 or 2)

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

your cancer has spread to other areas of the body (M1)
you have mixed small cell or non small cell lung cancer (NSCLC)
you have a collection of fluid between the sheets of tissue which cover the lungs and the heart (malignant pleural effusion or pericardial effusion)
you have had radiotherapy to your chest unless it was radiotherapy to treat breast cancer
you are going to have more than 20GY of radiotherapy to your lungs (your doctor can tell you more about this)
you are having cancer treatment that reaches your whole body (systemic)
you have had another cancer in the past 5 years unless it was an early cancer (carcinoma in situ of the cervix, bladder and breast or basal or squamous cell skin cancer that have been successfully treated

Medical conditions

You:

have an active infection
are sensitive to nivolumab, ipilimumab or anything they contain
have an autoimmune disease and you need to take drugs that damp down your immune system (immunosuppressants) such as steroids
have lung problems such as interstitial lung disease or fibrosis
have had an experimental treatment in the past 3 weeks
take an amount of drugs that are a concern for the trial team
have HIV
have hepatitis B or hepatitis C
are pregnant or breastfeeding
have any other medical condition or mental health problem that the trial team think could affect you taking part

Trial design

This is an international phase 2 trial. Researchers need around 325 people from Europe to take part.

This trial is in 2 parts. First, you go into part 1 and you might be able to join part 2 afterwards.

Part 1 (standard treatment)

Everyone has the standard treatment. The 1st part of the standard treatment is chemoradiotherapy. You have:

4 treatment cycles of chemotherapy with etoposide and cisplatin or carboplatin
radiotherapy twice a day for 3 weeks or radiotherapy once a day for 6 weeks

You then have prophylactic cranial irradiation (PCI). You have 10 radiotherapy treatments (fractions) in total.

Your doctor can tell you more about the standard treatment. It takes around 3 months in total.

After treatment, you have a CT scan. Doctors want to find out how well the standard treatment worked. You:

go into the 2nd part of the trial if your cancer stayed the same or got better
stop the trial if your cancer got worse (your doctor will tell you which other treatments you might be able to have if this happens)

Part 2

This part of the trial is randomised. Everyone taking part is put into 1 of the following groups by computer:

nivolumab and ipilimumab (experimental arm)
no more treatment (observation arm)

Neither you nor your doctor are able to decide which group you are in.

You have nivolumab as a drip into a vein. It takes about 30 minutes each time you have it. You have it:

every 3 weeks for 9 weeks
then every 2 weeks for up to a year

You also have ipilimumab as a drip into a vein. You have it every 3 weeks for 9 weeks. It takes about 90 minutes each time you have it.

You have no further treatment if you go into the observation group. Your doctor will see you regularly to check how you are.

Blood tests

You have extra blood tests as part of this trial. Researchers want to look at the levels of certain proteins (biomarkers Open a glossary item

) that can tell how well the treatment is working.

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

The research team might also ask you to have blood tests for future research studies. You don’t have to agree to this if you don’t want to. You can still take part in this trial.

Tissue sample

The trial team might ask to use a tissue sample of your cancer taken when you were diagnosed. Researchers want to store your tissue sample and use it in the future studies to learn more about lung cancer.

They may also ask you to have a biopsy Open a glossary item

if your cancer gets worse. You don’t have to agree to this if you don’t want to. You can still take part in this trial.

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

physical examination
blood tests
a PET-CT scan or a CT scan
an MRI scan of your brain

During the 1st part of the trial, you see the trial doctor every 3 weeks. You have regular blood tests and physical examinations.

During the 2nd part of the trial, you see the trial doctor every 3 weeks for 9 weeks. You then see them every 2 weeks for up to a year. You may see the trial doctor less often if you go into the observation group.

You have a CT scan after you finish the standard treatment. You then have a CT scan every:

9 weeks for up to 18 months
then every 12 weeks (3 months) for up to 2 years
then every 6 months for 2 years

You have the last CT scan about 5 years after the start of the trial.

Side effects

The trial team monitor you during the time you have treatment 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 the trial. The most common side effects of nivolumab and ipilimumab are:

thyroid problems (your thyroid may not produce enough hormones) causing tiredness and weight gain
loss of appetite
headaches
diarrhoea
skin rashes and itching
feeling or being sick
tiredness (fatigue)
high temperature (fever)
pain in your joints and stomach
inflammation of your bowel (colitis)