A trial of dalotuzumab with irinotecan for rectal cancer that has spread

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

Cancer type:

Bowel (colorectal) cancer

Rectal cancer

Status:

Closed

Phase:

Phase 2

This trial is looking at a drug called dalotuzumab alongside irinotecan for cancer of the back passage (rectum) that has spread to other parts of the body.

If rectal cancer spreads to another part of the body, you may have a chemotherapy drug called irinotecan and a drug called cetuximab. Cetuximab is a type of biological therapy called a monoclonal antibody. These can seek out cancer cells by looking for particular proteins.

In this trial, researchers are looking at another monoclonal antibody called dalotuzumab. Everybody taking part has irinotecan. Some people have cetuximab with it, some have dalotuzumab.

Some bowel cancers have a change (a mutation Open a glossary item ) to a gene called K-RAS. We know from research that cetuximab doesn't help people who have this mutation, so the researchers need to test for this.

Before you can take part in this trial, they will ask your permission to get a sample of your cancer that was removed when you had surgery or a biopsy Open a glossary item . They will test this in the laboratory to see if it has a normal K-RAS gene. They will also measure the levels of 2 markers called IGF-1 and IGF-2. You can only take part in this trial if you have high levels of IGF-1, low levels of IGF-2 and a normal K-RAS gene.

The aim of the trial is to see if the combination of irinotecan and dalotuzumab helps people with rectal cancer more than irinotecan and cetuximab.

Who can enter

You may be able to enter this trial if

You have cancer that started in your rectum, has spread to another part of your body and is getting worse despite having chemotherapy with oxaliplatin and irinotecan (your cancer must have got worse during chemotherapy, or within 3 months of finishing treatment)
Tests show that your tumour has a normal K-RAS gene, high levels of the marker IGF-1, and low levels of IGF-2
You have at least 1 area of cancer that is big enough to be seen and measured on a scan
You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
You have satisfactory blood test results
You are at least 18 years old
You are willing to use 2 reliable forms of contraception during the trial and for a month afterwards (3 months for men) if there is any chance you or your partner could become pregnant

You cannot enter this trial if you

Have cancer that has spread to your brain or spinal cord
Have diabetes that is not well controlled with medication
Have had chemotherapy or biological therapy in the last 2 weeks (or earlier if you have not fully recovered from side effects, unless they are very mild)
Have had surgery in the last 3 weeks
Have had radiotherapy in the last 2 weeks, unless it was radiotherapy for symptoms
Have had another experimental drug in the last month (or earlier if there is any chance some of the drug could still be in your body)
Stopped irinotecan previously due to bad side effects - other than due to tiredness (fatigue) or after taking it for a long period of more than 4 months
Have already had drugs that target receptors for insulin like growth factor (IGF-1), or for a growth factor called EGF (your doctor can confirm this)
Are known to be very sensitive to any of the drugs in the trial
Have had any other type of cancer, apart from carcinoma in situ of the cervix, basal cell skin cancer or prostate cancer that was contained in the prostate gland, had a PSA level lower than 1 and was successfully treated at least 5 years ago or your doctor thinks there is a very low risk of it coming back
Have a build up of fluid in your tummy (ascites ) or around your lungs (pleural effusion ) that is causing symptoms – you can take part if you have had one of these problems but it has been successfully treated
Have any other medical condition that the trial team think could affect you taking part
Use illegal drugs or drink an amount of alcohol that the trial team are worried about
Are known to be HIV positive
Are having treatment for hepatitis B or C
Are pregnant or breastfeeding

Trial design

This phase 2 trial will recruit about 70 people. It is a randomised trial. The people taking part are put into treatment groups by a computer. You will be told which group you are in, but neither you nor your doctor will be able to decide which group you are in.

You have treatment in 6 week cycles.

People in group A have irinotecan every 2 weeks and dalotuzumab once a week
People in group B have irinotecan every 2 weeks and cetuximab once a week

Dalotuzumab with irinotecan for rectal cancer that has spread trial diagram

You have these drugs through a drip into a vein. As long as you don’t have any bad side effects, you can carry on having the treatment for as long as it helps you.

Hospital visits

You see the trial team and have some tests before you start treatment. The tests include

Physical examination
Blood tests and urine tests
Heart trace (ECG )
Hearing test
CT scan

During the trial treatment, you go to hospital once a week. You have regular blood tests and you have a CT scan every 6 weeks.

People having dalotuzumab have another hearing test during the first cycle of treatment to check for any signs of hearing loss.

When you finish treatment, you see the trial team, and have more blood tests and a CT scan. You see the trial team again 2 weeks and 4 weeks later. They will examine you and ask about any symptoms you have and any side effects from the treatment. You also have more blood tests.

They will ask if a nurse can phone you every 3 months to see how you are. This follow up is optional – you don’t have to agree to this if you don’t want to.

Side effects

As dalotuzumab is a new drug, there may be side effects we don’t know about yet. In earlier trials, when people had dalotuzumab on its own, the side effects included

High sugar levels in the blood
Tiredness (fatigue) and weakness
Feeling sick
Weight loss

When people had dalotuzumab at the same time as chemotherapy, the side effects included

Stomach pain
Diarrhoea
Sickness
Pain and redness around your mouth
Painful swelling of fingernails and toenails
Tiredness and weakness
Hair loss
Rash, itching, dry or red skin
Loss of appetite and weight loss
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Changes to the way your liver works
High blood sugar levels
Low levels of magnesium in the blood
Constipation
Heartburn
Dry mouth
Swelling in your stomach or intestines
Muscle twitching
Dizziness
Taste changes
An allergic reaction
Numbness, aches, pain or cramps
Tingling in your hands or feet
Changes to your nails
Redness and swelling of the palms of your hands or soles of your feet