A trial looking at the drugs durvalumab and tremelimumab for cancer of the food pipe

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

Cancer type:

Oesophageal cancer

Secondary cancers

Status:

Closed

Phase:

Phase 1/2

This trial is for people with cancer of the food pipe (oesophageal cancer) who are going to have chemotherapy for the 1st time.

More about this trial

Treatment for oesophageal cancer depends on where the cancer is and whether it has spread. You might have:

chemotherapy
radiotherapy
chemotherapy together with radiotherapy (chemoradiotherapy)
surgery to remove all or part of the food pipe (oesophagus)

In this trial, doctors are looking at 2 new drugs called durvalumab (MEDI4736) and tremelimumab. 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 recognises them and kills them. Durvalumab and tremelimumab seek out 2 different proteins.

Researchers think that durvalumab and tremelimumab may help your immune system attack the cancer and stop them from growing.

There are 6 groups in this trial:

people with oesophageal cancer that has spread to other parts of the body (cohort A and cohort B)
people with oesophageal cancer who are going to have surgery to try to cure their cancer (cohort C, C-FLOT, D and D2)

Your doctor can tell you which group (cohort) you are suitable for before you join this trial. The treatment you have depends on the cohort you join.

The main aim of this trial is to find out whether it is safe to have durvalumab, tremelimumab and chemotherapy or radiotherapy.

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 this trial if all of the following apply. You:

have oesophageal cancer that has spread to other parts of the body or you have oesophageal cancer and your doctor thinks that you can have surgery to try to cure the cancer
are going to have chemotherapy for the 1st time, or you have had chemotherapy but you didn’t get the full dose
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 a satisfactory heart rate
are at least 18 years old
are willing to use reliable contraception during treatment and for up to 6 months after the last dose of durvalumab and tremelimumab if there is any possibility that you or your partner could become pregnant

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

have cancer spread to your brain unless it is stable and you have had treatment for it at least 4 weeks ago (your doctor can tell you more about this)
have cancer spread to your central nervous system and doctors think that you can have treatment for it such as radiotherapy
have had tremelimumab, durvalumab or any other similar drugs
have had treatment with a drug called sorivudine, brivudine or any other similar drug
can’t have full dose chemotherapy for treatment of your oesophagal cancer

Medical conditions

You:

still have moderate or severe side effects from earlier treatment
have had a major surgery in the past month
have had an experimental drug as part of a clinical trial in the last 4 weeks
have heart problems such as high blood pressure or angina that isn’t controlled, an irregular heartbeat or your heart can’t pump blood around the body properly (congestive heart failure)
have problems with your stomach such as inflammation of the lining of the stomach (gastritis) or an ulcer
have lung problems such as pneumonitis or interstitial lung disease
have bowel problems such as Crohn’s disease or inflammation of the bowel (colitis)
have had an autoimmune disease in the last 2 years apart from vitiligo, Grave’s disease or psoriasis that hasn’t needed systemic treatment in the past 2 years
have problems with your nerves (neuropathy)
have had an organ transplant from a donor (allogeneic organ transplant)
have a condition which means you are likely to bleed (bleeding diathesis)
have had a disease called sarcoidosis syndrome
have HIV
have an active infection
have hepatitis B or hepatitis C
have tuberculosis (TB)
have low levels of an enzyme called dihydropyrimidine dehydrogenase (DPD deficiency)
have any other serious medical condition or mental health problem that the trial team thinks could affect you taking part

Other
You:

are pregnant or breastfeeding
are allergic to any of the drugs used in this trial
are planning to give blood during this trial or for up to 6 months after the last dose of durvalumab and tremelimumab

Trial design

This is a phase 1/2 trial. Researchers hope that around 75 people from the UK will take part.

There are 6 groups (cohorts) in this trial:

people with oesophageal cancer that has spread to other parts of the body (cohort A and cohort B)
people with oesophageal cancer who are going to have surgery to try to cure their cancer (cohorts C, C-FLOT, D, and D2)

Your doctor can tell you which cohort you are in before you join this trial.

Cohort A

This group is divided into 2 groups: cohort A1 and cohort A2.

People taking part in A1 have 2 treatments with durvalumab alone. You have it as a drip into a vein. You have it in the first week of treatment and then after 2 weeks.

People taking part in A2 have durvalumab and tremelimumab as a drip into a vein on the 1st day of treatment. And have a second dose of durvalumab alone after 2 weeks. This cohort is now complete.

Then everyone has durvalumab and the chemotherapy drugs oxaliplatin and capecitabine. You have durvalumab, oxaliplatin and capecitabine as cycles of treatment. Each cycle takes 3 weeks. You have up to 6 treatment cycles in total.

You have each treatment cycle in the following way. You:

have durvalumab as a drip into a vein every 2 weeks for about 4 months
have oxaliplatin as a drip into a vein every 3 weeks for about 4 months
take capecitabine tablets every day for about 4 months

Cohort B

The treatment you have if you are in this group depends on what the researchers find in the first 2 groups (Cohorts A1 and A2). You can have durvalumab and the chemotherapy drugs oxaliplatin and capecitabine. Or durvalumab, tremelimumab, oxaliplatin and capecitabine.

Cohort C

You have 2 treatments with durvalumab alone. Then you have 2 cycles of treatment with durvalumab, oxaliplatin and capecitabine. You:

have durvalumab as a drip into a vein every 2 weeks for two and a half months
have oxaliplatin as a drip into a vein every 3 weeks for two months
take capecitabine tablets every day for 6 weeks

You have surgery after you finish the 2 treatment cycles of durvalumab, oxaliplatin and capecitabine. You have surgery in the same way as if you weren’t taking part in this trial. Your doctor can tell you more about this and what to expect.

After you recover from surgery, you might have more durvalumab. You can have it for up to 6 months.

Cohort C-FLOT

You have 2 treatments with durvalumab alone. Then you have 4 treatments with FLOT (5-fluorouracil, leucovorin, oxaliplatin and docetaxel) and durvalumab. You:

have durvalumab as a drip into a vein every 2 weeks for two months
have docetaxel, oxaliplatin and leucovorin as a drip into a vein, followed by the 5-fluorouracil as a drip into a vein over a 24-hour period. This will be repeated every 2 weeks, for two months.

About 6 to 8 weeks after you finish treatment, you have surgery. You have surgery in the same way as if you weren’t taking part in this trial. Your doctor can tell you more about this and what to expect.

About 3 months after surgery, you might have more treatment with durvalumab alone, FLOT alone, or durvalumab in combination with FLOT. Your study doctor will decide which treatment you will get. You can have the additional treatment for up to 6 months.

Cohort D
You have durvalumab as a drip into a vein every 2 weeks for a month. you then have chemotherapy with paclitaxel and carboplatin as a drip into a vein once a week, together with radiotherapy (chemoradiotherapy) for 5 weeks. After chemoradiotherapy, you have another durvalumab treatment.

About 6 to 8 weeks after you finish chemoradiotherapy and durvalumab, you have surgery. You have surgery in the same way as if you weren’t taking part in this trial. Your doctor can tell you more about this.

About 3 months after surgery, you might have more treatment with durvalumab. You can have it for up to 6 months.

Cohort D2

You have durvalumab as a drip into a vein every 2 weeks for a month. You will then have chemotherapy with paclitaxel and carboplatin as a drip into a vein once a week, together with radiotherapy (chemoradiotherapy), for 5 weeks. You continue to have durvalumab every 2 weeks together with chemotherapy and radiotherapy.

About 3 months after surgery, you might have more treatment with durvalumab. You can have it for up to 6 months.

Blood tests

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

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

Tissue sample

The trial team ask to take tissue samples (biopsy) of your cancer before the start of treatment and then:

after 4 weeks of treatment
after surgery (if you have this)
at the end of treatment

Doctors want to look at the genes and at how the cancer changes during treatment.

Saliva sample and photographs

If you are in group C, C-FLOT, D, or D2, the trial team will ask to take saliva samples and photographs of your cancer before the start of treatment and then:

after 4 weeks of treatment
after surgery
at the end of treatment

Doctors want to look at how the cancer changes during treatment. If you agree to this, the photographs will be taken at the same time as your tumour biopsy.

Hospital visits

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

physical examination
blood tests
urine test
pregnancy test (if applicable)
heart trace (ECG)
CT scan or PET-CT scan

During treatment, you see the trial doctor regularly. How often you see them depends on the group (cohort) you are in. You have blood tests, urine tests and a physical examination each time you see them.

You have a CT scan or PET-CT scan at set times during the trial. You continue to have treatment for as long as it works and the side effects aren’t too bad.

When you finish treatment, you see the doctor after 2 weeks. You then see them after:

6 weeks
3 months
4 months

After 4 months, the trial team will phone you every 6 months for 3 years.

Side effects

The trial team monitor you during the time you have treatment and afterwards. Durvalumab and tremelimumab are new drugs so there might be side effects we don’t know about yet. 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 durvalumab and tremelimumab are:

diarrhoea
skin problems such as dry skin, rashes and itching
increase in the levels of liver enzymes (this is usually mild and unlikely to make you feel unwell)
bleeding
pain
tiredness (fatigue)
tummy (abdominal) pain
a build up of fluid causing swelling
infections such as pneumonia
feeling or being sick
loss of appetite
breathlessness and cough
high temperature (fever)
changes in the levels of salts and minerals in your body