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

Please note this trial is no longer recruiting patients.

This trial is looking at a drug called EZN-2208, with or without cetuximab for bowel cancer that has spread to another part of the body.

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 are looking at a new drug called EZN-2208. It is made by joining SN38 to a substance called a glycol. This process is called pegylation. By doing this, the SN38 stays active in your body for longer and you may get more benefit from it. Some people will have EZN-2208 alone, some people will have EZN-2208 and cetuximab, some will have irinotecan and cetuximab.

We know from research that cetuximab does not help people whose cancer cells have a change (a mutation) to a gene called K-ras. Before you can take part in this study, you must agree to have a sample of your cancer tested for this gene. People who are found to have the K-ras mutation will not have cetuximab.

The aim of the trial is to see if EZN-2208 helps people with advanced bowel cancer

In combination with cetuximab for cancer that has a normal K-ras gene
On its own for cancer with an abnormal K-ras gene

Recruitment

Start 12/06/2009

End 30/06/2011

Phase

Phase 2

Who can enter

You can enter this trial if you

Have bowel cancer that has spread into surrounding tissue or to another part of your body and cannot be removed with surgery
Have already had the chemotherapy drugs irinotecan, oxaliplatin and 5FU (or a similar drug), and your cancer has got worse during this treatment or within the next 3 months
Have at least one area of cancer that can be seen and measured on a scan
Have satisfactory blood test results
Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
Are willing to use reliable contraception during the trial if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have had more than 2 other types of treatment for advanced bowel cancer after which your cancer has got worse
Have cancer that has spread to your brain and you need to have steroids or radiotherapy to control symptoms (you can take part if you have cancer that has spread to your brain but has been successfully treated, no longer causes symptoms and you don’t need steroids)
Have already had cetuximab, panitumumab or similar drugs, unless you were then found to have an abnormal K-ras gene, or you had cetuximab after surgery to try to stop your cancer coming back and it was more than a year before your cancer started growing again
Have had chemotherapy, immunotherapy or any other cancer treatment in the last 3 weeks (6 weeks if you had a drug called mitomycin C)
Have not recovered from the side effects of other cancer treatment (apart from hair loss) unless they are very mild
Have had major surgery in the last 3 weeks
Have had an experimental drug as part of another clinical trial in the last month
Have had another cancer in the last 5 years apart from non melanoma skin cancer or cervical cancer that has been cured with surgery
Have AIDS or a long term infectious disease
Have any other medical condition that the trial doctors think could affect you taking part
Are pregnant or breastfeeding

Trial design

This is a phase 2 trial. It will recruit about 220 people. The treatment you have will depend on K-ras testing of your cancer. If you have a mutated K-ras gene, you will be in group A. If you have a normal k-ras gene you will be put into either group B or group C. Neither you nor your doctor will be able to decide which of these 2 groups you are in. This is called randomisation.

People in group A have EZN-2208 alone
People in group B have EZN-2208 and cetuximab
People in group C have irinotecan and cetuximab

People in group A have treatment in 4 week periods called treatment cycles. In each cycle they have EZN-2208 once a week for 3 weeks, followed by a week without any treatment.

People in group B also have 4 week cycles of treatment. They have cetuximab once a week for 4 weeks and EZN-2208 once a week for the first 3 weeks of each treatment cycle.

People in group C have 3 week cycles of treatment. They have cetuximab and irinotecan once a week for the first 2 weeks of each cycle, then cetuximab alone in the 3rd week.

You have all 3 drugs through a drip into a vein

EZN-2208 takes about an hour each time
Cetuximab takes about 2 hours the first time you have it and about an hour each time after that
Irinotecan takes about an hour and a half each time

Treatment is expected to last 4 months, but this may be shorter or longer, depending on your response to treatment.

The trial team will ask your permission to take some extra blood samples during the trial. And they may ask to get an extra sample of tissue that was removed when you had surgery or a biopsy. The researchers will use these samples to look at how genes may affect the way people respond to treatment or the side effects they have. They will also look for substances called biomarkers that could help them check for gene changes. This may help doctors in the future to work out which people are most likely to benefit from the trial drug. If you don’t want to give these samples for research, you don’t have to. You can still take part in the trial.

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include

Physical examination
Blood tests
CT scan, PET scan or X-ray

Depending on which group you are in, you go to hospital 3 or 4 times in each treatment cycle.

During treatment and at certain times after you finish treatment, you will have blood tests and a scan or X-ray. The trial team will follow your progress every 3 months for at least 6 months. This may be at hospital appointments, or they may contact you by phone to see how you are.

Side effects

As EZN-2208 is a new drug, there may be side effects we don’t know about yet. From earlier trials, the researchers know the most common side effects include