A study looking at cediranib (AZD2171) and AZD6244 with chemotherapy and radiotherapy for rectal cancer (DREAM)

You can enter this trial if

• You have been diagnosed with rectal cancer that has grown into (or very near to) the membrane covering the outside of the bowel, or is stage T3 and less than 5cm from your anus
• Your doctors don’t think it would be possible to remove all the cancer and a border of healthy tissue around it (clear margins) with surgery as your first treatment
• Your doctors do think it will be possible to treat your cancer with radiotherapy
• You have satisfactory blood test results
• You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
• You are willing to use reliable contraception during the trial if there is any chance you or your partner could become pregnant
• You are at least 18 years old

You cannot enter this trial if you

• Have cancer that has spread somewhere else in the body (metastatic cancer)
• Have already had chemotherapy or radiotherapy for rectal cancer
• Have had major surgery to your chest or tummy (abdomen) in the last 2 weeks, or any other surgery if the wound has not completely healed
• Are not able to have surgery
• Have another condition that means you may not be able to have radiotherapy such as ulcerative colitis, Crohn’s disease or a fistula
• Have a blockage in the bowel (bowel obstruction) or an infection in the pelvis
• Have a condition called DPD deficiency (which means you cannot have certain types of chemotherapy)
• Have high blood pressure that cannot be controlled with medication, or a heart problem that is a cause for concern
• Have an infection that cannot be controlled, or any other medical condition that could affect you taking part in the study
• Cannot absorb tablets for any reason, including sickness that cannot be controlled with medication and inflammatory bowel disease
• Have or have had any other type of cancer
• Are known to be HIV, hepatitis B or hepatitis C positive
• Are pregnant or breastfeeding

Also,

• If you are known to be sensitive to cediranib, or have had recent bleeding problems or blood clots, you cannot take part in the cediranib study
• If you have already had a MEK inhibitor, you cannot take part in the study of AZD6244

The trial will recruit up to 56 people all together. Some people will be involved in the study of cediranib, some will be involved in the study of AZD6244. This will depend on when you join the trial.

Everybody taking part will have

• Radiotherapy for 5 weeks
• Capecitabine tablets everyday for 5 weeks during the radiotherapy

Both the trial drugs are tablets that you swallow each day. Whichever drug you have, you start taking it 10 days before your radiotherapy starts, and take it every day until the last day of radiotherapy.

The first few patients taking part in each study will have a low dose of either cediranib or AZD6244. If they don’t have any serious side effects, the next patients will have a higher dose. And so on, until they find the best dose of each drug to give. This is called a ‘dose escalation study’.

You have a CT scan or MRI scan 8 weeks after finishing chemoradiotherapy. If this shows that your cancer can be removed, you will have surgery between 2 and 4 weeks later.

The doctors will take some extra blood samples during the trial. And they will get a sample of the tissue that was removed when you had a biopsy to diagnose your cancer. After taking your study drug for about a week, you have a test called a flexible sigmoidoscopy. The doctor puts a thin tube into your back passage and takes another sample of cancer tissue.

The researchers will use these samples to look for substances they can measure that help them tell more about a disease or how a treatment is working – these are called biomarkers. They hope that in the future, biomarkers may help them to work out who is most likely to benefit from the trial drugs.

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

• Physical examination
• Blood and urine tests
• Heart trace (ECG)
• CT scan
• MRI scan

People taking part in the AZD6244 study will also have

• Eye tests
• Heart ultrasound (echocardiogram)

You go to hospital

• The day you start taking your study drug
• Once or twice in the next 10 days
• Every day (from Monday to Friday) during 5 weeks of radiotherapy
• 2, 4 and 8 weeks after finishing chemoradiotherapy

The trial team will ask some people taking part to have some extra scans before, during and after treatment. This is to see how the growth of the cancer changes during treatment. If you are in the cediranib study, these will be ‘Dynamic Contrast Enhanced’ MRI scans (DCE-MRI). If you are in the AZD6244 study, you may be asked to have DCE-MRI scans and PET scans.

A member of the trial team will contact you by phone to check how you are 4 months after finishing your chemoradiotherapy. You have follow up appointments every 6 months for 2 years and then one more a year later.

As AZD6244 and cediranib are quite new drugs, there may be some side effects we don’t know about. The possible side effects that are known include

• Diarrhoea
• Feeling or being sick
• Tiredness (fatigue)
• An increase in your blood pressure
• Changes to results of tests that show how well your liver is working (liver function tests)

Other possible side effects of AZD6244 include

• Skin rash
• Swelling of the face or other parts of the body (extremities)
• Shortness of breath
• Blurred vision

Other possible side effects of cediranib include

• Redness or soreness on the palms of your hands or soles of your feet (hand and foot syndrome)
• Muscle weakness
• Headache
• Dry or sore mouth
• Hoarseness
• Protein in the urine
• Bleeding
• Changes to the way your thyroid gland works
• Heart changes

There is more information about the side effects of rectal radiotherapy and capecitabine on CancerHelp UK.