A trial of CXD101 and nivolumab for a certain type of advanced bowel cancer (CAROSELL)

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

Cancer type:

Bowel (colorectal) cancer

Secondary cancers

Status:

Closed

Phase:

Phase 1/2

This trial is looking at a new drug called CXD101 alongside nivolumab for bowel cancer that has spread elsewhere in the body.

It is for people who have a certain type of bowel cancer called microsatellite stable.

Bowel cancers have different types of changes in the DNA. A small number of bowel cancers have DNA changes called microsatellite instability. Most bowel cancers do not have these changes and are called microsatellite stable. This is the most common type of advanced bowel cancer.

More about this trial

Bowel cancer that has spread elsewhere in the body is called advanced or metastatic bowel cancer. The usual treatment is chemotherapy. You might have a combination of chemotherapy that includes oxaliplatin and irinotecan. Sometimes chemotherapy stops working, so doctors want to improve treatment.

In this trial, they are looking at a new drug called CXD101 alongside another drug called nivolumab.

CXD101 is a drug that blocks substances in the body called histone deacetylases (pronounced dee-as-et-isle-azes). Cells need these to grow and divide. Blocking them may stop cancer growing. Drugs that block these enzymes are called histone deacetylase inhibitors or HDAC inhibitors.

Nivolumab is a type of immunotherapy. It uses the immune system to help kill cancer cells. It is already used to treat several different types of cancer but not this type of bowel cancer.

Researchers want to see if CXD101 and nivolumab works for people with advanced bowel cancer.

The aims of the trial are to:

find the safest dose of CXD101 in combination with nivolumab
find out how well CXD101 and nivolumab work together
learn more about the side effects of CXD101 in combination with nivolumab

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 bowel cancer that has spread elsewhere in the body
have bowel cancer that is microsatellite stable and mismatch repair proficient (MMR-P), the doctors test a tissue sample to check for this, if a sample is not available from when you were diagnosed, you may need to have biopsy to test for this
have had a first course and a second course of chemotherapy for bowel cancer that included the chemotherapy drugs oxaliplatin and irinotecan
have cancer that the doctors can measure on a scan
are well enough to be up and about for at least half the day (performance status 0,1 or 2)
have satisfactory blood test results
are willing to use reliable contraception during treatment and for 5 months afterwards if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

have cancer that has spread to the brain or surrounding tissues, spinal cord compression or uncontrolled fits (seizures)
have had treatment with HDAC inhibitors in the past such or targted drugs such as pembrolizumab or nivolumab
have had chemotherapy, radiotherapy or an experimental drug in the 4 weeks before joining the trial
have had any other cancer in the past unless it had been successfully treated and you haven’t had treatment for this in the last 5 years

Medical conditions

You:

have had problems with your heart in the last 6 months such as a heart attack, angina that isn’t well controlled with medication or severe congestive heart failure
have an inflamed heart muscle (myocarditis)
have had a serious lung problem that caused breathing problems in the last 6 months
have an infection that needs treatment with antibiotics or antiviral medication
have side effects from past treatments that aren’t getting better
have certain bowel conditions such Crohn’s disease or a blockage in your bowel
are taking medications that dampen down the immune system
have a lung condition called pneumonitis
have a problem with how your thyroid gland works that isn’t controlled with medication
have an autoimmune disease such as rheumatoid arthritis
have hepatitis B, hepatitis C or a type of hepatitis called immune hepatitis
have any other medical condition or mental health problem that the trial team think would affect you taking part

Other

You:

are pregnant or breastfeeding
are allergic to CXD101 or anything it contains
have had a live vaccine within 30 days of staring trial treatment

Trial design

This is a phase 1/2 trial. It is taking place in the UK. It is in 2 parts. The researchers hope to find about 52 people in total. Everyone has CXD101 and nivolumab.

Part 1

Part 1 is now open. In part 1, researchers are looking at the best dose of CXD101 to have in combination with nivolumab. The researchers need about 12 people to join part 1.

The first few people taking part will have a low dose of CXD101 alongside a standard dose of nivolumab. The next few people will have a higher dose if there weren’t serious side effects in the earlier patients at the lower dose.

Part 2

Part 2 isn’t open to people yet. But it will be by early 2019. In part 2, the researchers plan to test the best dose of CXD101 alongside nivolumab in a larger number of people. They hope about 37 people will join part 2.

Treatment

CXD101 is a white capsule. You take them twice a day, for five days in a row as directed.

You have nivolumab as a drip into a vein. Everyone has the same dose of nivolumab.

You have treatment in cycles. The first day of each treatment cycle is called day 1. For CXD101, day 1 is every three weeks (or 21 days). For nivolumab it is every two weeks (or 14 days).

You:

take CXD101 on day 1 to 5
have a break from day 6 to 21

You complete a medication diary and record the days you take CXD101 and how many you take.

You have nivolumab every 2 weeks on day:

You have treatment for as long as it is working and the side effects aren’t too bad. You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.

Samples for biomarker research

The researchers will look at tumour tissue samples from past surgeries or biopsies. The trial team will ask you to give another sample if you haven’t had a biopsy in the last year. They plan to use these to look for biomarkers. Biomarkers are diagnostic test results which if they can be linked to drug effects, could be used to predict in future the best treatment for a patient (precision medicine).

Hospital visits

You see a doctor and have some tests before you can take part. These include:

physical examination
blood samples
urine samples
heart trace (ECG)
CT scan or MRI scan

You might have to give a tissue sample if there isn’t one available. This is to find out if you have microsatellite stable bowel cancer.

You have nivolumab in the hospital outpatient department. You shouldn’t need to stay overnight. You take your CXD101 tablets at home. Apart from the first day of each treatment cycle when you take them at the hospital.

At each hospital visit you see the doctor for a check up and you have blood tests every 3 weeks.

You have a CT scan every 6 weeks, these continue unless your cancer gets worse. You continue to have scans if you stop treatment, but your cancer hasn’t got worse.

When you stop treatment, you have a check up with the trial team about 9 weeks later. The trial team will continue to follow you up every 3 months to see how you are getting on.

Side effects

As CXD101 is a new drug, there might be some side effects we don’t know about yet. The trial team will monitor you during the time you have treatment and you’ll have a phone number to call if you are worried about anything.

Only a few people have had CXD101 so far. The possible side effects include:

tiredness (fatigue)
feeling sick
a drop in the number of blood cells causing an increased risk of infection, tiredness and breathlessness, bruising and bleeding

The most common side effects of nivolumab include: