A trial of AZD5305 for certain types of solid cancers that are getting worse (PETRA)
Cancer type:
Status:
Phase:
This trial is looking at AZD5305 on its own or in combination with other cancer treatments for some 
A solid cancer is any cancer apart from the blood cancers. Blood cancers include leukaemias, lymphomas and myeloma.
This trial is for people whose cancer has spread to nearby tissues or to another part of the body.
More about this trial
Cancer that has spread is called . Researchers think AZD5305 might help people with certain types of advanced cancer.
AZD5305 is a type of called a PARP inhibitor. PARP is a protein found in our cells, it stands for poly-ADP ribose polymerase. It helps damaged cells to repair themselves.
As a cancer treatment, PARP inhibitors stop the PARP from doing its repair work in cancer cells. This causes the cancer cell to die.
You might have a PARP inhibitor if you have ovarian, breast, pancreatic or prostate cancer.
AZD5305 is a little different from currently available PARP inhibitors. We know from early research that it’s better at targeting certain PARP proteins.
In this trial everyone has AZD5305. And some people also have one the following:
- chemotherapy
- a cancer drug called trastuzumab deruxtecan
- a cancer drug called datopotamab deruxtecan
Trastuzumab deruxtecan is a type of drug called an antibody drug conjugate. It is trastuzumab with a chemotherapy drug attached to it. Deruxtecan is the chemotherapy like drug. Trastuzumab finds and attaches to the HER2 protein on the cancer cell. Deruxtecan is then released into the cancer cell damaging or killing the cell. This stops the cancer from growing.
Datopotamab deruxtecan is a combination of 2 drugs. Datopotamab is a monoclonal antibody. It attaches to a protein called TROP2 on the cancer cells. It then releases deruxtecan into the cancer cell. Deruxtecan or DXd is the chemotherapy part of the drug. It kills or damages the cancer cell.
The main aims of the trial are to find out:
- the best dose of AZD5305 to give on its own
- more about the side effects
- what happens to AZD5305 in the body
- how well AZD5305 works in combination with the other cancer treatments in this trial
Who can enter
Please note, there are several treatment groups so the entry conditions for this trial are complex.
Each group has specific entry conditions and we haven’t listed them all. The trial team check if you are suitable to join the trial and which group you might join. They can tell you more about this.
Who can take part
The group you join depends on your cancer type.
Group 1 is open to women with ovarian cancer
Group 2 is for people with triple negative breast cancer or breast cancer that is . This group is now closed to recruitment.
Group 3 is for people who have ovarian cancer, triple negative breast cancer or breast cancer that is HER2 negative. This group is now closed to recruitment.
Group 4 is for people who one of the following types of cancer that is HER negative:
- breast cancer
- non small cell lung cancer
- bowel (colorectal cancer)
- bladder cancer
- ovarian cancer
- stomach cancer
- biliary cancer
- cervical cancer
- womb cancer
adenocarcinoma of the pancreas
Group 5 is for people who have one of the following types of cancer:
- non small cell lung cancer
- ovarian cancer
- small cell lung cancer
- breast cancer
- womb cancer
- prostate cancer
As well as having one of the above cancer types, you may be able to take part if all of the following also apply. You:
- have cancer that has grown into nearby tissues or has spread elsewhere in the body
- have cancer that is getting worse despite treatment
- have cancer that your doctor can see and measure on a scan or they can assess it another way. For example, by having a blood test for ovarian or prostate cancer.
- have a
sample of cancer tissue available for the trial team to do some tests on or you are willing to give a new sample - have certain genetic changes (
mutations ) on your cancer cells. The trial doctor can tell you more about this and which groups this applies to. - have had at least one
PARP inhibitor in the past if you join a part of the trial looking at the best dose of AZD5305 - are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- are willing to use reliable contraception during treatment and for a period after if there is any chance you or your partner could become pregnant
- have satisfactory blood test results
- are at least 18 years old
Who can’t take part
These are the main exclusion conditions.
Cancer related
You cannot join this trial if any of these apply. You:
- have cancer that has spread to the brain or spine or you have pressure on the spine (
spinal cord compression ). You might be able to join if this isn’t causing symptoms, you have had treatment and it is stable. - have had mitomycin C or a
nitrosoureas within 6 weeks of the first dose of trial treatment - have had any cancer treatment including chemotherapy, radiotherapy or an experimental drug within 3 weeks of the first dose of trial treatment or the treatment hasn’t cleared your body
- have had a targeted drug including an
immunotherapy within 4 weeks of starting trial treatment - have had radiotherapy to a large area of your body within 4 weeks of starting trial treatment or in the last 2 weeks if you had it to control cancer symptoms such as pain
- have already had a PARP inhibitor if you join a part of the trial that isn’t looking at the best dose of AZD5305 to have. The trial doctor can tell you about this.
Medical conditions
You can’t take part if any of the following apply. You
- have a significant
heart problem such as a heart attack in the last 6 months or a heart condition that isn’t well controlled with medication. Your doctor checks your heart before you join the trial. - have had a stroke or mini stroke within 6 months of joining the trial
- take medication that might affect your heart rhythm. Your doctor will know this.
- are having
steroid treatment unless it is a low dose. Your doctor will know this. - have ongoing side effects from past treatments unless they are mild. This doesn’t include hair loss.
- have an active bleeding problem or you have a higher risk of bleeding. Your doctor will know this.
- have problems with your
digestive system such as having part of your bowel removed, ulcerative colitis, feeling or being sick or diarrhoea. This could affect how well you absorb medication. - take medication that affects the CYP enzymes
- have
myelodysplastic syndrome or a type of blood cancer called acute myeloid leukaemia - have had major surgery in the month before starting trial treatment
- have HIV, an active hepatitis B or hepatitis C infection or any severe infection that needs treatment
- are having any other cancer treatment or any other treatment that you can’t have if you take part in the trial. The team check this before you join.
- are taking part in another trial unless it doesn’t involve a treatment
- took part in another trial of AZD5303 even if you didn’t have this treatment
- have any other medical condition or mental health problem that the trial team think will affect you taking part
Other
You can’t take part if any of the following apply. You:
- have had a live
vaccine or bacterial vaccine such as the tuberculosis vaccine in the month before starting trial treatment. Please note the current approved COVID-19 vaccines are not live. - are allergic to AZD5305 or anything it contains
- are pregnant or breastfeeding
| As well as the above there are specific entry conditions for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial. |
Trial design
This is a phase 1/2 trial. The trial is taking place worldwide. In total the team need 880 people to take part. The group you are in depends on your cancer type and which groups are open. There are 5 groups:
- Group 1 is looking at AZD5305 on its own - open only to women with ovarian cancer
- Group 2 is looking at AZD5305 in combination with paclitaxel – closed to recruitment
- Group 3 is looking at AZD5305 in combination with paclitaxel. Some people also have carboplatin – closed to recruitment
- Group 4 is looking at AZD5305 in combination with trastuzumab deruxtecan - open
- Group 5 is looking at AZD5305 in combination with datopotamab deruxtecan - open
Testing for gene changes in cancer cells
To begin with, the team check a sample of cancer you gave in the past. Some people might need to give a new sample. The team are looking for certain genetic changes on your cancer cells. Your cancer cells may need to have a gene change for you to be able to take part. The trial team can tell you more about this.
Having AZD5305
AZD5305 is a tablet. You take them once a day, every day. The dose you have depends on when you join the trial. You have treatment for as long as it is working and the side effects aren’t too bad.
You have . Each cycle of treatment is 28 days. Before the first cycle, you go to hospital for a single dose of AZD5305. The team then monitor you closely for 3 days. AZD5305 may cause your heart to beat fast or low blood pressure. You have a machine to check your blood pressure and heart rate at home. Or you have these checked at the hospital.
Some people may also have a 24 hour ECG monitor fitted. Once the team are satisfied that you haven’t developed a heart problem, you continue with the rest of the trial.
Group 1 - open
In this group you have AZD5305 on its own. The team hope about 22 people from the UK will join part 1.
There are 2 parts. Part 1 is looking at the best dose of AZD5305. Part 2 is testing this dose level in a larger group of people.
The first few people taking part have a low dose of AZD5305. The next few people have a higher dose if they don’t have serious side effects. And so on, until the doctor finds the best dose. This is a dose escalation study.
When they find the best dose, they test this in more people.
Group 2 – is now closed to recruitment
In group 2 you have AZD5305 and paclitaxel.
Group 3 – closed to recruitment
In group 3 you have AZD5305 and paclitaxel. Some people also have carboplatin.
Group 4 – open
In group 4 you have AZD5305 and trastuzumab deruxtecan (T-DXd). There are 2 parts. Part 1 is looking at the best dose of AZD5305 to have alongside trastuzumab deruxtecan. Part 2 is testing this dose level in more people.
You have AZD5305 as described above. You have trastuzumab deruxtecan as a drip into a vein. You have it once every 3 or 4 weeks.
Group 5 – open
In group 5 you have AZD5305 and datopotamab deruxtecan (Dato-DXd). There are 2 parts. Part 1 is looking at the best dose of AZD5305 to have alongside datopotamab deruxtecan. Part 2 is testing this dose level in more people.
You have AZD5305 as described above. You have datopotamab deruxtecan as a drip into a vein. You have it once every 3 or 4 weeks.
For all parts of the trial
You have treatment for as long as it is working and the side effects aren’t too bad. You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.
Research samples
You give some extra blood samples when you have treatment. The team can tell you exactly when you give these. Where possible you have them at the same time as your routine bloods. Researchers will use these samples to:
- find out what happens to AZD5303 in the body
- check how AZD5303 is working
- look for tumour markers and small pieces of cancer DNA in the blood (
ctDNA) - look for
biomarkers to work out why treatment works for some and not others - look at genes in cancer cells
The trial doctor may also ask you give extra tissue samples. You don’t have to agree to give these samples if you don’t want to. You can still take part in the rest of the trial.
Hospital visits
You see the doctor and have tests before you can take part. These include:
- blood tests
- a
physical examination - heart trace (
ECG ) - heart scan (
echocardiogram ) or MUGA scan - ultrasound scan
- bone scan if you have breast cancer or prostate cancer
- CT scan or MRI scan
You have some of your treatment at the hospital on the day care ward. You see the doctor during treatment at regular times. This is to see how you are and for some tests. You may have a few overnight stays. The team can tell you more about this.
You have an MRI scan or CT scan every 8 weeks.
When you finish treatment you see the doctor 1 month later for a check up.
The team then follow you up every 3 months. You might see them at a routine hospital appointment or they may call you to see how you are getting on.
Side effects
The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.
AZD5305 is a new drug. This is the first time that people are having AZD5305 so we don’t know about all the side effects.
The possible side effects that we know about so far include:
- a drop in the number of blood cells causing an increased risk of infection, tiredness, breathlessness, bruising or bleeding
- fast heartbeat or changes to your heart rhythm
- low blood pressure
- developing
myelodysplastic syndromes that can develop into a blood cancer called acute myeloid leukaemia - fertility problems in men
- problems with eyesight
Please note, if you have any fast or uneven heartbeats, light headedness, giddiness, shortness of breath, fainting, or chest pain you should contact your trial doctor immediately.
During treatment you should avoid eating large amounts of grapefruit and Seville oranges or other products that contain these fruits.
The most common possible side effects of trastuzumab deruxtecan include:
- feeling or being sick
- tiredness (fatigue)
- hair loss
- constipation
- loss of appetite
- a drop in the number of blood cells causing an increased risk of infection, tiredness, breathlessness, bruising or bleeding
- cough
- stomach (abdominal) pain
- infections of the upper respiratory tract
- headache
- indigestion
- dry eye
- dizziness
- sores in or around your mouth
- liver changes
- difficulty breathing or lung problems
- severe nose bleeds
- low potassium in the blood
- skin rash
- high temperatures (fever)
- swelling of lower legs or hands
The most common possible side effects of datopotamab deruxtecan include:
- feeling or being sick
- inflammation of the lining of the digestive tract
- hair loss
- tiredness (fatigue)
- loss of appetite
- diarrhoea
- skin rash
- a drop in the number of
red blood cells - dry eye
The trial doctor will talk to you about all the side effects of treatment before you agree to take part.
We have more information about:
Location
Recruitment start:
Recruitment end:
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.
Chief Investigator
Dr Adam Sharp
Supported by
AstraZeneca
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
