A trial looking at olaparib and AZD5363 for people with cancer that has come back or spread elsewhere in the body (ComPAKT)

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

Cancer type:

All cancer types

Status:

Closed

Phase:

Phase 1

This trial is looking at a combination of 2 drugs called olaparib and AZD5363 for people who have a solid tumour for which there is no other treatment available. A solid tumour is any type of cancer other than leukaemia Open a glossary item . The trial is supported by Cancer Research UK.

More about this trial

Olaparib is a drug you take by mouth. It targets and blocks a protein called PARP (it is a PARP inhibitor). PARP repairs damage to DNA Open a glossary item in our cells. Doctors hope that if they can stop PARP working, cancer cells won’t be able to repair themselves and will die. AZD5363 is another drug you take by mouth. It stops signals that cancer cells use to divide and grow.

Research in the laboratory has shown that olaparib and AZD5363 together might stop cancer growing. In this trial, researchers want to see if this drug combination helps people by shrinking advanced cancer.

The trial is in 2 parts. People with any type of solid tumour can join the first part of the trial. In the second part, the researchers will be looking for people with certain gene changes including people who have changes (mutations) to genes called BRCA1 or BRCA2.

The aims of the trial are to

Find the highest dose of AZD5363 you can have with olaparib
Learn more about the side effects of both drugs
See what effects the drugs have on the body

Who can enter

You may be able to join this trial if all of the following apply

You have a solid tumour (any type of cancer except leukaemia) that has come back or spread elsewhere in your body
There is no suitable standard treatment available for you
You have an area of cancer that the doctor can measure
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 over 18 years of age
You are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance you or your partner could become pregnant (women who could possibly become pregnant must also use reliable contraception for 4 weeks before joining the trial)

You cannot enter this trial if you

Have cancer that has spread to your brain or is pressing on your spinal cord (spinal cord compression) unless you are free from symptoms and have not taken steroids in the last 4 weeks
Have had radiotherapy (apart from radiotherapy for symptoms) in the last 4 weeks
Have had hormone therapy in the last 4 weeks (if you are having hormone therapy for prostate cancer you may be able to take part)
Have had surgery, immunotherapy or chemotherapy in the last 4 weeks. If you have had chemotherapy with either nitrosoureas or Mitomcyin C this must have been in the last 6 weeks
Are taking part in any other trial looking at an experimental drug, or have had another experimental drug in the last 4 weeks
Have not recovered from the side effects of other treatment unless they are very mild – the trial doctors can advise you about this
Have any type of myelodysplastic syndrome
Have diabetes or much higher than normal levels of sugar in your blood
Have a high level of protein in your urine (your doctor can check for this)
Have had a heart attack in the last 6 months or have any other heart condition that is a cause for concern (the trial doctors can advise you about this)
Have a problem with your digestive system or uncontrolled sickness that may affect how you absorb drugs (your doctor can advise you about this)
Are unable to swallow tablets or capsules
Are known to be allergic or very sensitive to olaparib or AZD5363, or to similar drugs (or anything they contain)
Have had any medication that affects the CYP3A4 enzyme in the last 2 weeks (your doctor can advise you about this)
Have had St John’s Wort in the last 3 weeks
Have a condition that means you are at risk of bleeding (bleeding diathesis)
Have an active infection with HIV, hepatitis B or hepatitis C
Have another serious medical condition or mental health problem that the trial team think could affect your taking part
Are pregnant or breastfeeding

Trial design

This is a phase 1 trial. It is in 2 parts. For part 1 the researchers need about 12 to18 people to take part. For part 2 they will need about 40 people.

The aim of the first part of the trial is to find out the best dose of AZD5363 that you can have with olaparib. You will be put into 1 of 2 groups. People in both groups take olaparib twice a day throughout the trial. Then

One group have AZD5363 twice a day for 4 days each week (with 3 days off)
One group have AZD5363 twice a day for 2 days each week (with 5 days off)

Olaparib is a tablet and AZD5363 is a capsule. From November 2014 all patients having AZD5363 will have this as a tablet. Your dose of AZD5363 will be increased twice if you don’t have any bad side effects.

Once the researchers have established the best dose of AZD5363, they will move into the second part of the trial. The aim of this part is to find out more about how the combination of the 2 drugs works. The researchers will be looking for people with certain gene changes, including people who have changes to genes called BRCA1 or BRCA2.

The researchers will work out the best way to take AZD5363 in the first part of the trial. If you join the second part, the researchers will tell you when to take both drugs.

The researchers may ask you to have a biopsy Open a glossary item before the treatment starts and again a couple of weeks after starting treatment. These samples may help researchers learn more about how the drugs work. If you don’t wish to have these biopsies, you don’t have to. You can still take part in the trial.

You can have treatment

For as long as it is helping you and your cancer has not grown
Until you decide you don’t want to continue with the trial
Until your trial doctor feels its best for you to stop the trial

Hospital visits

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

Physical examination
Blood tests
Urine tests
CT scan or MRI scan
Heart trace (ECG )
Heart scan (echocardiogram ) or MUGA scan

You may also have a bone scan.

You need to go to hospital regularly during treatment. During your hospital visits you will have a physical examination and blood and urine tests to check your general health. The doctors will also ask you to have a mouth (buccal) swab.

You have a heart trace (ECG) on the 1st day of treatment, at the end of the 1st week, then every 3 weeks.

You have a heart scan (an echocardiogram or MUGA scan) after 3 weeks.

You may be in a group where the researchers are looking more closely at the levels of the drugs in your body. This is called pharmacokinetics Open a glossary item . Before you have your first dose of the drugs, your doctor will pluck 8 of your eyebrow hairs so they can test the hair follicle (the base of the hair). The doctors may take more hair follicles during treatment to check the levels of the drugs in your body. If you do not have enough eyebrow hair you can still take part in the trial. You will also have regular blood tests and may need to stay overnight.

If you agreed to have a sample of your cancer (biopsy Open a glossary item ) taken just before the start of the trial, you may also have a second biopsy. This will be a couple of weeks after starting treatment.

About every 9 weeks you will have a CT or MRI scan so that the doctors can measure your cancer. You may also have some blood tests to check for tumour markers Open a glossary item .

AZD5363 can increase the levels of sugar in your body. The trial team will ask you to do a urine test twice a week to check for sugar.

When you finish the trial treatment you go to hospital about 4 weeks later for a check up and a repeat of the tests you had before you started treatment.

Side effects

As olaparib and AZD5363 are new drugs, there may be side effects we don’t know about yet. The known side effects for both drugs are

Tiredness (fatigue)
Loss of appetite
Skin rash
Feeling or being sick
Diarrhoea
Indigestion
A sore mouth
An effect on your liver causing yellowing of your skin or eyes, itching or tummy pain (jaundice )
Heart problems, including a faster heart beat and a change to the heart rhythm
Tummy (abdominal) pain
An effect on your kidneys

AZD5363 can also

Cause an allergic reaction including an itchy rash, high temperature (fever) and swelling of your face. You must tell your doctor straight away if you have any of these
Increase in the amount of sugar in your blood
Make you more sensitive to sunlight

Olaparib can also cause