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A trial of AZD5363 with docetaxel and prednisolone for prostate cancer that has spread and is no longer responding to hormone therapy (ProCAID)
This trial is looking at a drug called AZD5363 alongside chemotherapy to see if it helps men with prostate cancer that has spread to another part of the body and isn’t responding to hormone therapy. The trial is supported by Cancer Research UK.
More about this trial
If prostate cancer spreads to other parts of the body, doctors often treat it with hormone therapy. But after a while, this can stop working. If this happens, you may have chemotherapy and steroids. But researchers are looking for new treatments to help men in this situation. In this trial they are looking at a drug called AZD5363 alongside chemotherapy and steroids.
AZD5363 is a type of biological therapy. It stops signals that cancer cells use to divide and grow.
The aims of the trial are to
Who can enter
You may be able to enter this trial if you
- Have prostate cancer that has spread to another part of your body, is not responding to hormone therapy and PSA tests, a CT scan or a bone scan show that your cancer is getting worse
- Are going to have docetaxel chemotherapy
- Have very low levels of the hormone
- Have stopped any other prostate cancer treatment at least 2 weeks ago (you can take part if you’re having hormone therapy to keep your testosterone level low)
- Have cancer that didn’t get smaller within 6 weeks of stopping the drugs bicalutamide or flutamide
- Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
- Have satisfactory blood test results
- Are able to swallow tablets
- Are at least 18 years old
- Are willing to use reliable contraception during the trial and for a month afterwards if there is any chance your partner could become pregnant
You cannot enter this trial if you
- Have already had chemotherapy for prostate cancer (you may have had other drugs such as bisphosphonates, denosumab, abiraterone, enzalutamide or up to 6 treatment cycles of docetaxel)
- Have cancer that has spread to your brain or caused spinal cord compression unless this was treated successfully
- Have had radiotherapy to more than about a third of your
bone marrow(your doctor can advise you about this)
- Have had another experimental drug in the last month
- Have had any other type of cancer if your doctor thinks there is a 30% or more chance of it coming back within 2 years
- Have type 1 or type 2
diabetesthat requires medication (you may be able to take part if you have type 2 diabetes that is well controlled with diet alone)
- Have a problem with your
digestive systemthat means it may be difficult for you to absorb the trial drug
- Have had a heart attack in the last 6 months or have certain other heart problems (the trial team can advise you about this)
- Have low blood pressure that can’t be controlled with medication
- Have protein in your urine
- Have taken other medication that affects body substances called cytochrome P (CYP) enzymes in the last 2 weeks (the trial team can advise you about this)
- Have taken St John’s wort in the last 3 weeks
- Haven’t recovered from the side effects of other treatment (apart from hair loss) unless they are very mild
- Are known to be very sensitive to AZD5363 or similar drugs
- Have already had drugs that target proteins called AKT, PI3K or mTOR (your doctor can advise you about this)
This phase 1/2 trial will recruit about 150 men. The trial is in 2 parts.
In part 1, the researchers are looking for the highest dose of AZD5363 that you can safely have with docetaxel and prednisolone. In this part of the trial, everybody has AZD5363. The first few men taking part will have a low dose of AZD5363. If they don’t have any serious side effects, the next few patients will have a higher dose. And so on, until they find the best dose to give. This is called a dose escalation study.
Please note - this part of the trial has finished and patients are now being recruited to part 2.
In part 2, they are comparing AZD5363 with a dummy drug (
Everybody joining this part of the trial has docetaxel and prednisolone. Half the men also have the highest safe dose of AZD5363 that was found in part 1. The other half will have a dummy drug.
In both parts of the trial you have chemotherapy in 3 week periods called cycles of treatment. You have up to 10 cycles of chemotherapy.
You have docetaxel through a drip into a vein on the 1st day of each treatment cycle. It takes about an hour each time. You take prednisolone tablets every day.
You take AZD5363 (or the dummy drug) throughout your treatment, starting on the 2nd day of the 1st cycle of chemotherapy. AZD5363 comes in capsules that you swallow. You take the capsules twice a day for 4 days, followed by a 3 day break.
You should take the capsules 12 hours apart and try to take them at about the same time each day. You mustn’t eat or drink anything apart from water for at least 2 hours before taking the capsules and for at least 1hour afterwards.
If they are helping you, you can carry on taking the capsules after you finish having chemotherapy, as long as you don’t have bad side effects.
The trial team will give you a diary to help you to remember the days when you need to take the capsules.
They will also ask you to complete a questionnaire a number of times during the trial and when you finish treatment. It will ask about any pain you have, how it is being managed and how it is affecting your daily activities.
You see the trial team and have some tests before you start the trial treatment. The tests include
- Physical examination
- Heart trace (
- Heart scan (
- Blood tests
- CT scan or MRI scan
- Bone scan
If you join phase 1 of the trial, you go to hospital 5 times in each of the first 2 cycles of treatment. You have a number of blood tests at these visits. On some days, the trial team will ask you not to eat anything for 8 hours before arriving at the hospital and not to take your capsules until you’ve had a blood test.
From cycle 3 onwards, you go to hospital at least once every 3 weeks for as long as you have the trial treatment.
If you join phase 2, you go to hospital twice in the 1st cycle of treatment and then once every 3 weeks after that.
Everybody has regular blood tests and some more heart traces throughout the trial. The trial team will explain what will happen at each hospital visit.
When you finish treatment, you see the trial team and have more blood tests and scans. You then continue to see them every 6 weeks until your cancer starts to get worse or you start another type of treatment.
As AZD5363 is a new drug, there may be side effects we don’t know about yet. In trials so far, the most common side effects have included
- Feeling or being sick
- An increase in your blood sugar level
- Tiredness (fatigue)
- Loss of appetite
- Tummy (abdominal) pain
- Sore mouth
- High temperature (fever)
The most common side effects of docetaxel include
- A drop in blood cells causing an increased risk of infection, tiredness and breathlessness
- Feeling sick
- Sore mouth
- Numbness and tingling in your hands and feet (peripheral neuropathy)
- An allergic reaction
- A rash
- Fluid retention causing swollen ankles
The most common side effects of prednisolone include
- Stomach discomfort
- Fluid retention
- An increase in your blood sugar level
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Dr Simon Crabb
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
University Hospital Southampton NHS Foundation Trust
This is Cancer Research UK trial number CRUK/12/042.