A trial looking at ceralasertib for ovarian and endometrial clear cell cancers (ATARI)

Cancer type:

Cervical cancer
Ovarian cancer
Womb (uterine or endometrial) cancer

Status:

Open

Phase:

Phase 2

This trial is for people with certain subtypes of gynaecological cancers that have come back after treatment. It is open to people with ovarian or endometrial clear cell cancers and certain types of other rare gynaecological cancers particularly endometrioid, carcinosarcoma or cervical cancers.

You pronounce ceralasertib as se-ra-la-sir-tib.

Cancer Research UK supports this trial.

More about this trial

Ceralasertib is a targeted drug Open a glossary item called an ATR inhibitor. In healthy cells ATR proteins help repair damage to DNA Open a glossary item before the cells divide. From laboratory research we know it can kill cancer cells that have a change (mutation Open a glossary item) in the ARID1A gene Open a glossary item

Certain rare types of ovarian, endometrial and other gynaecological cancers particularly clear cell types often have this change in the ARID1A gene. Researchers think that ceralasertib might work for people with these types of cancer. 

Research shows that having an ATR inhibitor with other targeted drugs might also kill cancer cells without the change in the ARID1A gene. In this trial the team are looking at ceralasertib with olaparib or durvalumab. 

Olaparib is a PARP inhibitor. It works by stopping the protein PARP from working. The protein PARP helps damaged cells repair themselves. Doctors already use olaparib to treat ovarian cancer and some other types of cancer. 

Durvalumab is a type of immunotherapy Open a glossary item called a monoclonal antibody Open a glossary item. It helps the immune system to find and fight cancer.

There are 5 groups in this trial. 

Depending on which group you are in you have one of the following treatments:

  • ceralasertib on its own
  • ceralasertib with olaparib
  • ceralasertib with durvalumab

Of the 5 groups, groups 1, 2 and 3 are closed to recruitment. Groups 4 and 5 are open to recruitment.

The aims of this trial are to find out:

  • how well ceralasertib works for ovarian or endometrial clear cell cancers and other gynaecological cancers
  • how well the combination of ceralasertib and olaparib works for these cancers 
  • how well the combination of ceralasertib and durvalumab works for endometrial cancers

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you. 

There are 5 groups in this trial. Each group might have certain entry conditions to join that group.

 

Who can take part

You may be able to join this trial if you have one of the following cancers that has continued to get worse or came back after treatment (recurred):

And all of the following apply. You:

  • have available a sample of tissue (biopsy Open a glossary item) from when you were diagnosed at first or when your cancer came back that the trial team can ask for. If this isn’t available, you are willing to give a new sample.
  • have had a scan that shows your cancer has got worse since your last treatment and before you join the trial
  • have had at least 1 treatment with a platinum drug Open a glossary item such as carboplatin
  • have an area of cancer that can be seen and measured on a scan
  • are fully active but might not be able to do heavy physical work (performance status 0 or 1)
  • have satisfactory blood test results
  • can swallow tablets or capsules
  • are willing to use reliable contraception during treatment and for a month after if there is any chance you could get pregnant
  • are at least 18 years old 

For groups 4 and 5 

The following must also apply. You:

  • have had an immunotherapy such as a PD-1, PD-L1 or CTLA-4 inhibitor for at least 6 weeks. Your doctor will know this.
  • have no ongoing side effects. If you had certain side effects from the treatment you might not be able to join the trial. Your doctor will know which side effects these are.
  • weigh more than 30kg (4st 7lb)

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

  • had ceralasertib or another ATR inhibitor treatment. This depends on the type of cancer you have. Your doctor will know about this. 
  • had a PARP inhibitor such as olaparib. This depends on the type of cancer you have. Your doctor will know about this.
  • had chemotherapy within 3 weeks of starting the trial treatment
  • had a targeted drug Open a glossary item within a month of starting the trial treatment
  • had an immunotherapy Open a glossary item within 6 weeks of starting trial treatment
  • had bevacizumab within a month of starting trial treatment
  • had radiotherapy to relieve symptoms (palliative radiotherapy) within 3 weeks of starting trial treatment. For radiotherapy that included 30% or more of the bone marrow it is 4 weeks. If the treatment area was wide it is 4 weeks. Your doctor will know about this. 
  • have another cancer or had a cancer that needed treatment in the past 3 years apart from cervical intraepithelial neoplasia Open a glossary item and non melanoma skin cancer Open a glossary item
  • have ongoing side effects from previous treatment apart from hair loss (alopecia)
  • have pressure on your spine (spinal cord compression Open a glossary item) unless it has been treated and it has been stable for 4 weeks
  • have cancer spread to the brain or spinal cord unless it has been treated, isn’t getting worse and have not had steroids for at least 4 weeks before joining the trial 
  • have a myelodysplastic syndrome Open a glossary item (MDS) or acute myeloid leukaemia Open a glossary item (AML) or symptoms of these conditions 

For groups 4 and 5

You cannot join if any of the following also apply. You:

  • are having any other treatment such as chemotherapy, a targeted drug or hormone treatment. This is apart from having hormone treatment for another reason other than cancer such as hormone replacement therapy (HRT).
  • have very low levels of blood cells for more than 4 weeks that was due to previous treatment. You doctor will know this.
  • have another cancer. This is apart from successfully treated non melanoma skin cancer Open a glossary item, a type of melanoma skin cancer called lentigo maligna Open a glossary item or a carcinoma in situ Open a glossary item. You could join if you had a cancer more than 5 years ago that was treated with the aim to cure and there has not been any sign of it since. 

Medical conditions 
You cannot join this trial if any of these apply. You:

  • have had an experimental drug as part of a clinical trial in the 4 weeks before joining the trial
  • are taking medications such as certain antibiotics or herbal products such as St John’s Wort that affect the CYP enzymes. You might be able to take part if you can stop taking them. Your doctor can tell you about this.
  • have a blockage in your bowel or you have symptoms of a bowel blockage within 6 weeks of joining the trial
  • have blood in your urine and your doctor think this could affect you taking part
  • have heart problems Open a glossary item or have had in the past 6 months. This includes irregular heartbeats, chest pain (angina) that isn’t stable, a heart attack or heart failure.
  • low blood pressure when you lie or sit down and your doctor think it could affect you taking part
  • have an inherited Open a glossary item syndrome called ataxia telangiectasia Open a glossary item
  • have had major surgery within 4 weeks of joining the trial,  for minor surgery within 2 weeks before joining the trial
  • have had a bone transplant with bone marrow from another person (allogeneic transplant Open a glossary item) or a double umbilical cord blood transfusion
  • have taken corticosteroids at a dose of more than 10mg of prednisolone a day within 4 weeks of joining the trial
  • have had blood cell growth factors Open a glossary item such as G-CSF or a blood transfusion within 2 weeks of joining the trial. You have had a red blood cell growth factor called erythropoietin Open a glossary item within 4 weeks of starting trial treatment or you might need it during treatment.
  • have HIV, hepatitis B or hepatitis C
  • have a problem with your liver Open a glossary item, kidneys or lungs Open a glossary item that your doctor think could affect you taking part
  • have an active problem with bleeding
  • have ongoing problem with feeling sick (nausea) or being sick (vomiting) or with your digestive system Open a glossary item that could affect how well medication is absorbed
  • have an active infection caused by bacteria, fungus or virus that needs treatment that affects your whole body
  • have fits (seizures) that isn’t controlled by medication
  • have any other medical condition or mental health problem that the doctor or trial team think could affect you taking part

For groups 4 and 5 

You cannot join this trial if any of these also apply. You:

  • have had an organ transplant Open a glossary item and you are taking medication that damps down the immune system Open a glossary item
  • have or had an autoimmune disease Open a glossary item or an inflammatory disease within the past 3 years. This is apart from certain ones that your doctor will know about.
  • have or had problems that affect how well your immune system works
  • are taking or have taken medication that damps down the immune system. This is apart from nasal sprays, creams, inhalers, local injections or a small dose of steroids. 

Other
You cannot join this trial if any of these apply. You:

  • are allergic to any of the drugs or their ingredients used in this trial
  • are pregnant or breastfeeding

Trial design

This is an international phase 2 trial

You agree to the trial team asking for a piece of cancer tissue from when you were first diagnosed or from when your cancer came back. If this isn’t available you must agree to give a new tissue sample. 

This is to confirm what type of cancer you have. For people with endometrial clear cell cancer, ovarian clear cell cancer or endometriosis-related clear cell cancer it is also to look for certain changes (mutations Open a glossary item and protein loss) related to the ARID1A gene Open a glossary item

There are 2 stages in this trial. The 2nd stage will open to recruitment if the results of the 1st stage look promising. 

In the 1st stage 10 people join each group. The team will ask more people to join if the treatment looks promising. 

Group 1
This group is now closed. It was for people with clear cell cancer of the ovaries, endometrium or endometriosis related and your cancer cells have the abnormal ARIDA1 protein. 

In this group they had ceralasertib on its own. 

Group 2
This group is now closed. It was for people with clear cell cancer of the ovaries, endometrium or endometriosis related and your cancer cells don’t have the abnormal ARIDA1 protein. 

In this group they had ceralasertib in combination with olaparib. 

Group 3
This group is now closed. It was for people with:

  • ovarian endometrioid
  • endometrial endometrioid
  • cervical cancer adenocarcinoma or squamous cell
  • ovarian carcinosarcoma
  • endometrial carcinosarcoma

Your cancer cells may or may not have the abnormal ARIDA1 protein. 

In this group they had ceralasertib and olaparib.

Group 4
In this group the team are looking for up to 58 people to join. 

This group is for people with:

  • endometrial cancer  clear cell
  • endometrial endometrioid
  • endometrial carcinosarcoma

And whose cancer cells have the abnormal ARIDA1 protein.

In this group you have ceralasertib and durvalumab.

Group 5
In this group the team are looking for up to 58 people to join. 

This group is for people with:

  • endometrial cancer  clear cell
  • endometrial endometrioid
  • endometrial carcinosarcoma

And whose cancer cells does not have the abnormal ARIDA1 protein.

In this group you have ceralasertib and durvalumab.

Treatment
Ceralasertib is a tablet. You take it at the same time each day. You swallow the tablets whole with a glass of water on an empty stomach. This means you can’t eat any food for 2 hours before taking them and within 1 hour after. 

Groups 4 and 5
You take 3 tablets of ceralasertib once a day for a week. You then have 3 weeks of not taking them. This is a cycle of treatment Open a glossary item. You then continue the cycle of treatment.

You have durvalumab as a drip into a vein once every 4 weeks. This is a cycle of treatment. 

In each group you continue to have treatment as long as it is working and the side effects aren’t too bad. 

Medicines and food to avoid
There are certain medications, herbal products and foods you shouldn’t have when taking ceralasertib. These include:

  • certain antibiotics
  • treatments for a fungal infection (anti fungal)
  • HIV medication
  • medication to stops fits (anti convulsant)
  • calcium channel blockers
  • anti depressants

You shouldn’t eat:

  • grapefruit
  • pomelos
  • star fruit
  • Seville oranges or anything made from them such as marmalade 

Your doctor will tell more about this. 

Research samples
You give extra blood samples during the trial. The team take these when you have your routine bloods taken. 

If you have fluid around your abdomen (ascites) due to your cancer, they will ask for samples of this during the trial. You do not have to agree to this. You can still take part in the trial.

Hospital visits

You see the doctor to have tests before taking part. These tests include:

  • a physical examination Open a glossary item
  • blood tests
  • urine test
  • heart trace (ECG)
  • a fresh tissue sample (biopsy) if a previous sample isn’t available 
  • CT scan or an MRI scan

You see the doctor regularly during treatment. This is for blood tests and to see how you are. 

You have a CT scan, an MRI scan or both every 8 weeks. 

You see the doctor at the end of treatment and then 3 months later for blood tests and to see how you are. And then every:

  • 8 weeks for a year
  • 12 weeks until your cancer starts to get worse or you start a new treatment

You have a scan every 8 weeks for the first year and then every 12 weeks.

During treatment if your cancer gets worse you stop treatment and are followed up every 3 months. 

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. 

Durvalumab can affect the immune system Open a glossary item. This may cause inflammation Open a glossary item and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects.

These side effects can happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for. 

If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy. 

 

Ceralasertib is a new drug and there might be side effects we don’t know about yet. The side effects we do know about are:

Ceralasertib might also make your skin more sensitive to sunlight. So it is best not to go out in the sunlight too often while having ceralasertib. 

An allergic reaction can happen with all drugs and this can be life threatening. Contact your doctor or the health advice line if you have any of the following that might signs of an allergic reaction:

  • trouble breathing
  • swelling of the face, mouth, lips, tongue, gums or neck

We have information on olaparib and durvalumab

Your doctor or a member of the trial team will talk to you about the possible side effects of ceralasertib and olaparib before you agree to join the trial.

Location

Bath
Edinburgh
Glasgow
London
Manchester

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Susana Banerjee

Supported by

AstraZeneca
Cancer Research UK
Institute of Cancer Research (ICR)
Lady Garden Foundation

Other information

This is Cancer Research UK trial number is CRUKE/18/014.

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

16452

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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