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.

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 before the cells divide. From laboratory research we know it can kill cancer cells that have a change (mutation ) in the ARID1A gene .

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 in the laboratory also showed having an ATR inhibitor with another targeted drug called a PARP inhibitor might also kill cancer cells without the change in the ARID1A gene.

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.

In this trial some people have ceralasertib on its own and some people have ceralasertib with olaparib.

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

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.

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):

ovarian cancer clear cell
endometrial cancer clear cell
endometriosis related clear cell
ovarian endometrioid
endometrial endometrioid
cervical cancer adenocarcinoma or squamous cell
ovarian carcinosarcoma
endometrial carcinosarcoma

And all of the following apply. You:

have available a sample of tissue (biopsy ) 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 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

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
had a PARP inhibitor such as olaparib
had chemotherapy within 3 weeks of starting the trial treatment
had a targeted drug within a month of starting the trial treatment
had an immunotherapy 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
have another cancer or had a cancer that needed treatment in the past 3 years apart from cervical intraepithelial neoplasia and non melanoma skin cancer
have ongoing side effects from previous treatment apart from hair loss (alopecia)
have pressure on your spine (spinal cord compression ) 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 (MDS) or acute myeloid leukaemia (AML) or symptoms of these conditions

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 blood in your urine and your doctor think this could affect you taking part
have heart problems 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 syndrome called ataxia telangiectasia
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 ) 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 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 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, lungs or kidney 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 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

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 and protein loss) related to the ARID1A gene.

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 there are 4 groups (cohorts). At the start 10 people join each group. The team will ask more people to join if the treatment looks promising.

Group 1A
This group is 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 you have ceralasertib on its own.

Group 1B
This group is 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 you have ceralasertib in combination with olaparib.

The researchers will only open this group if ceralasertib isn’t working for people in group 1A.

Group 2
This group is 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 you have ceralasertib in combination with olaparib.

Group 3
This group is 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 you have ceralasertib and olaparib.

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.

For group 1
People in group 1 take 2 tablets twice day for 2 weeks. You then have 2 weeks of not taking the tablets. Each 4 week period is a cycle of treatment Open a glossary item .

For groups 2 and 3
People in group 2 and 3 take 2 tablets of ceralasertib a day once a day for a week. You then have 3 weeks of not taking the tablets. This 4 week period is a cycle of treatment.

Olaparib is a tablet. You take 2 tablets twice a day every day. This should be at the same time each day. You swallow them whole with a glass of water. When you take olaparib with ceralasertib you have it on an empty stomach. When you take olaparib on its own you don’t have to take it on an empty stomach.

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.

Hospital visits

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

a physical examination
blood tests
urine test
heart trace (ECG )
a fresh tissue sample (biopsy) if a previous sample isn’t available

You see the doctor at the start of treatment and then during treatment at:

1 week
2 weeks
4 weeks
6 weeks
8 weeks
and then every 4 weeks while having treatment

This is for blood tests and to see how you are.

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

You see the doctor at the end of treatment and a month 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.

ceralasertib is a new drug and there might be side effects we don’t know about yet. The side effects we do know about is a drop in blood cells that might cause an increased risk of:

breathlessness
infection
bruising and bleeding

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.

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.