A trial of EZN-2208 for bowel cancer that has spread

Cancer type:

Bowel (colorectal) cancer

Colon cancer

Rectal cancer

Status:

Results

Phase:

Phase 2

This trial looked at a drug called EZN-2208, with or without cetuximab for bowel cancer. It was for people with cancer that had spread to another part of the body (advanced bowel cancer).

More about this trial

Doctors can treat advanced bowel cancer with a drug called cetuximab and chemotherapy. One of the chemotherapy drugs they often use is called irinotecan. The active part of irinotecan is called SN38.

In this trial, researchers looked at a new drug called EZN-2208. It is made by joining SN38 to a substance called a glycol. This process is called pegylation Open a glossary item . By doing this, the SN38 stays active in your body for longer and you may get more benefit from it. In this trial, some people had EZN-2208 alone, some people had EZN-2208 with cetuximab and some had irinotecan with cetuximab.

We know from research that cetuximab doesn’t help people whose cancer cells have a change (a mutation Open a glossary item ) to a gene called K-RAS. Before taking part in this trial, everyone agreed to have a sample of their cancer tested for this gene. People who were found to have the K-RAS mutation didn’t have cetuximab.

The aim of the trial was to see if EZN-2208 helped people with advanced bowel cancer, either with cetuximab for cancer that had a normal K-RAS gene, or on its own for cancer with an abnormal K-RAS gene.

Summary of results

The trial team found that EZN-2208 with cetuximab worked just as well as irinotecan and cetuximab. EZN-2208 on its own didn’t work for people whose cancer had an abnormal K-RAS gene.

This was a phase 2 trial. It recruited 211 people. It was a randomised trial. The people taking part were put into 1 of 3 treatment groups.

93 people with an abnormal K-RAS gene had EZN-2208 only
80 people with a normal K-RAS gene had EZN-2208 and cetuximab
38 people with a normal K-RAS gene had irinotecan and cetuximab

Trial Diagram

After treatment the researchers looked at how many people’s cancer had responded. This included people who had no sign of their cancer or whose cancer had shrunk after treatment. They found that with:

EZN-2208 no one’s cancer responded
EZN-2208 and cetuximab it was about 11 out of every 100 people (10.7%)
irinotecan and cetuximab it was about 14 out of every 100 people (14.3%)

Trial Diagram

The average number of months that people were alive and cancer free was:

just under 2 months for those who had EZN-2208 only
just under 5 months for those who had ENZ-2208 and cetuximab
just under 4 months for those who had irinotecan and cetuximab

The researcher looked at the overall average time that people lived after treatment. For those who had:

EZN-2208 only it was 5½ months
EZN-2208 and cetuximab it was just under 10 months
irinotecan and cetuximab it was just over 9 months

Trial Diagram

The most common side effects of EZN-2208 on its own were:

tiredness
a drop in white blood cells causing an increased risk of infection
diarrhoea
feeling or being sick
not having enough fluid in your body (dehydration)

The most common side effects of EZN-2208 and cetuximab were

a drop in white blood cells
skin rash
diarrhoea
not having enough fluid in your body
tummy (abdominal) pain
being or feeling sick

The most common side effects of irinotecan and cetuximab were:

a drop in white blood cells
diarrhoea
not having enough fluid in your body
skin rash

The trial team concluded that the combination of EZN-2208 and cetuximab was as good as irinotecan and cetuximab. EZN-2208 on its own didn’t help people whose bowel cancer had the change in the K-RAS gene. EZN-2208 was safe to use by itself and with cetuximab.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.