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A trial looking at AZD5363 and enzalutamide for advanced prostate cancer (RE-AKT)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
This trial is looking at AZD5363 and enzalutamide for men with prostate cancer that has spread and continued to grow despite having other treatment.
Enzalutamide is a type of hormone therapy that is used for men with advanced prostate cancer who have already had other types of hormone therapy and a type of chemotherapy called docetaxel. Researchers want to see if a having a new drug called AZD5363 alongside enzalutamide will help to control the growth of cancer for longer.
More about this trial
AZD5363 is a type of biological therapy. It stops signals that cancer cells use to divide and grow. There are 3 different parts to this trial. The first and third part have now closed to recruitment.
The second part aims to find out
- whether enzalutamide and AZD5363 work better than enzalutamide and a dummy tablet (placebo)
- more about the side effects of having enzalutamide and AZD5363 together
The third part recruited a group of men who had already had treatment with enzalutamide and whose cancer has continued to grow. The researchers hope to find out which men in particular will benefit from this treatment.
Who can enter
You may be able to join this trial if all of the following apply.
- You have adenocarcinoma of the prostate gland that has spread to other parts of your body (metastatic prostate cancer) and it is continuing to grow despite having treatment
- Your diagnosis was confirmed when you had surgery, or when a sample (biopsy) of your cancer was taken. If this is not the case, you will need to have a biopsy to confirm your diagnosis
- A sample of your cancer is available for the trial team to test for a fault in a gene called PTEN
- You have had hormone therapy with the aim of lowering the amount of testosterone in your body
- You have had at least 1 or 2 treatments with a group of chemotherapy drugs called taxanes
- You have had treatment with a drug called abiraterone (you must have had this treatment for at least 3 months)
- Have a PSA blood test result that is equal to or more than 10ng/ml
- Have satisfactory results from other blood tests
- Are well enough to be up and about for at least half of the day (performance status 0,1 and 2)
- You are willing to use contraception during the trial and for at least 1 year afterwards if you are sexually active and there is any chance your partner could become pregnant
- You are at least 18 years old
You cannot join this trial if any of these apply. You
- Have cancer that has spread to your brain
- Have already had treatment with drugs that block the action of cancer growth blockers such as P13K inhibitors, AKT inhibitors or mTOR inhibitors (your doctor can advise you about this)
- Have had surgery, chemotherapy, or treatment in a trial in the last 4 weeks
- Have had hormone therapy in the last 2 weeks, or in the last 6 weeks if you had a drug called bicalutamide (Casodex)
- Have had radiotherapy in the last 4 weeks (you can take part if you have had radiotherapy to just a small area of your body to control symptoms in the last 2 weeks)
- Have had any other anti cancer treatment in the last 4 weeks (there are some drugs that you can’t have taken in the last 2 weeks, the trial team can advise you about this)
- Have had any other cancer in the last 5 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated
- Are still having side effects from any anti cancer treatment, apart from hair loss or severe numbness and tingling in your hands and feet (peripheral neuropathy
- Have had fits (seizures) in the past, or you have a medical condition or injury which puts you at risk of having a fit (your doctor can confirm whether this applies to you)
- Have been diagnosed with diabetes or have high levels of sugar in your blood (you will have a blood test to check this)
- Have a condition which means your body cannot absorb the trial drug properly
- Have any other medical condition that the trial doctor thinks could affect your taking part
- Have had any medication that affects body substances called CYP enzymes in the last 2 weeks (with the exception of St John’s wort, which you should avoid for 3 weeks before the start of the trial). Your doctor can explain what this means in more detail
- Have certain heart problems such as a heart attack in the last 6 months or heart failure
- Have certain liver problems, such as cirrhosis of the liver or hepatitis
- Are unable to swallow tablets
As well as the above, men who join part 2 of the trial cannot take part if they have already had treatment with enzalutamide.
This is a phase 1/2 trial. It has 3 parts.
The first part is now closed to recruitment. Everyone had AZD5363 and enzalutamide. The first few people had a low dose of AZD5363. If they didn’t have any serious side effects the next few patients had a higher dose. And so on until the trial doctors found the best dose to give. This is called a dose escalation study.
Only the second part is now open to recruitment.
The second part of the trial is randomised. The researchers need 100 men to join. They are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither of you will know which group you are in. This is called a double blind trial.
- People in one group have enzalutamide and AZD5363
- People in the other group have enzalutamide and a dummy drug (placebo)
Everyone has the same dose of enzalutamide and the best dose of AZD5363 that was found in the first part of the trial. You have enzalutamide tablets once a day every day (with or without food).
You have AZD5363 or the dummy tablet twice a day for 4 days. Then no AZD5363 or dummy drug for the next 3 days. You should have these tablets on an empty stomach. So 1 hour before food or at least 2 hours after food.
All men in part 2 are asked to fill out a short questionnaire every 4 weeks during treatment and then 4 weeks after treatment has finished. This will ask you about any pain you have whether it is mild or severe.
Part 3 of the trial has now closed to recruitment.The researchers needed 18 men to join. Every man in this group had already had treatment with enzalutamide and their cancer has continued to grow despite this treatment.
Everybody in part 3 has enzalutamide and AZD5363. You have these drugs in the same way as described in part 2.
Whichever part of the trial you join, you have treatment for as long as your doctor thinks it is helping you, or you decide that you would like to stop treatment.
You will see the doctors and have some tests before you start treatment. The tests include
- Blood tests
- Urine sample collected over 24 hours
- Saliva test and a swab of the inside of your cheek (bucal swab)
- Physical examination
- Heart trace (echocardiogram)
- Heart scan or MUGA scan
- CT scan
- Bone scan
Men in part 3 have eight blood samples taken over the first 3 days of treatment. You also have hair samples taken at 3 to 4 different points during the trial. The researchers look at these blood tests, urine samples and hair samples to measure the levels of AZD5363 and enzalutamide in your body and to see what effect these drugs have on your body.
Men in part 2 will go to hospital 3 times in the first 4 weeks of treatment. Men in part 3 will visit hospital 9 times during the first 12 weeks of treatment. After these visits, everyone will go to hospital every 4 weeks until they finish treatment. You see a doctor at these appointments, who will ask you about any symptoms and you have further blood tests.
You may be asked not to eat anything for 8 hours before you go for your hospital appointment. And to wait to take your morning tablets until after you have had your blood tests. This applies to men in parts 2 and 3.
All men have a CT scan and bone scan every 12 weeks during treatment and some men will also have a scan at the end of treatment and 4 weeks after treatment has finished.
The most common side effects of AZD5356 include
- an increase in your blood sugar level
- tiredness (fatigue)
- feeling or being sick
- feeling short of breath
- redness and swelling of the mouth and lips
- dry itchy skin
The most common side effects of enzalutamide include
- hot flushes
The trial team will go through possible side effects and when you should contact them. They can prescribe treatments to manage and relieve these side effects.
We have more information about enzalutamide.
How to join a clinical trial
Professor Johann de Bono
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
Institute of Cancer Research UK
The Royal Marsden NHS Foundation Trust