A study looking at chemotherapy and APR-246 for women with ovarian cancer (EUTROC-PiSARRO)

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

Cancer type:

Ovarian cancer

Status:

Closed

Phase:

Phase 1/2

This study is for women who have a high grade (fast growing) cancer that has come back after previous treatment (recurrent cancer).

The study is for women who have:

These cancers are treated in the same way. So when we use the term ovarian cancer in this summary, we are referring to all 3.

More about this trial

Chemotherapy is the usual treatment for women with recurrent high grade ovarian cancer.

In this study doctors want to see if adding a new drug called APR-246 improves treatment.

APR-246 targets p53. p53 controls the way cells multiply. It should stop cancers growing. When it works normally it helps the chemotherapy drugs kill the cancer cells.

But p53 in cancer cells is often damaged (mutated) and so does not work normally. This may be part of the reason some cancers are resistant to certain chemotherapy drugs.

APR-246 may be able to re activate p53. So the chemotherapy should work better.

In this study everyone has 2 chemotherapy drugs often used to treat ovarian cancer

peglyated liposomal doxorubicin
carboplatin

Half the people taking part will also have APR-246.

The main aim of this study is to see if having APR-246 with chemotherapy improves treatment.

Who can enter

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

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

You have a high grade ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is positive for p53 (your doctors will check for this)
Your cancer came back between 6 months to 2 years after your 1st or 2nd course of chemotherapy that included a platinum drug
You have an area of cancer that can be seen and measured on a scan
You have satisfactory blood results
You are willing to use reliable contraception during the time of treatment and for 6 months afterwards if there is any chance you could become pregnant
You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
You are 18 years or older

You cannot join this study if any of these apply. You

Have cancer spread to your brain (brain metastases)
Have any serious side effects from previous treatment apart from hair loss. If you have numbness or tingling of your fingers or toes (peripheral neuropathy ) you may be able to take part, your doctor will let you know
Have had all the doses you can have of the drugs doxorubicin or epirubicin
Are having, or have had within 4 weeks of starting the study treatment, chemotherapy, radiotherapy, hormone replacement therapy or any experimental drug treatment unless these were to help with symptoms only
Have had major surgery within 6 weeks of starting in the study
Are having or need to have a live vaccine
Are having or will need to have phenytoin
Are allergic to carboplatin, any other platinum based drugs, mannitol, pegylated liposomal doxorubicin or anything they contain
Are not able to have a CT scan or an MRI scan for any reason
Have had an inflammation of the tissue that lines the inside of your abdomen (peritonitis) within 6 weeks of starting in the study
Have a blockage in your bowel (bowel obstruction)
Have a disease that narrows your veins or arteries (sub occlusive disease)
Have certain heart problems such as a heart attack in the last 6 months, heart failure, abnormal heart rhythm, problems with the way your heart pumps blood or with the flow of blood to your heart, a history of long QT syndrome (or it is in your family) or a disease of the membrane of the heart (pericardial disease)
Have any other cancer that needs treatment, unless it is a very early cancer
Have HIV
Have active hepatitis B or hepatitis C
Have any other serious medical condition or mental health problem that the trial team think could affect you taking part
Are pregnant or breastfeeding

Trial design

This is an international study. Doctors need about 400 people to take part from hospitals in the UK, Europe and the USA.

It is a phase 1b/2 study. Phase 1b has now completed. This information is about phase 2.

This study is randomised. The people taking part are put into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in.

• One group have peglyated liposomal doxorubicin, carboplatin and APR-246
• The other group have peglyated liposomal doxorubicin and carboplatin

Diagram for EUTROC-PiSARRO

Peglyated liposomal doxorubicin, carboplatin and APR-246
You have APR-246 as a drip into your vein. You have it once a day over 6 hours for 4 days. On the 4th day you have carboplatin and liposomal doxorubicin as well. You also have these as a drip into your vein. You then have a break for 24 days.

Each 28 day period is a cycle of treatment. If, after your first cycle, you have coped with the treatment you have another cycle of treatment. You can have up to 6 cycles of treatment.

You also have a blood test for the first 5 days of your first 2 cycles of treatment.

If you have any more cycles you have a blood test just on the first of the 4 days you have treatment.

Peglyated liposomal doxorubicin and carboplatin
You have carboplatin and liposomal doxorubicin as a drip into your vein. You then have a break for 27 days.

Each 28 day period is a cycle of treatment. If, after your first cycle, you have coped with the treatment you have another cycle of treatment. You can have up to 6 cycles of treatment.

To see what action the chemotherapy is having on your cancer you have a blood test the day after your treatment. This is only for the first 2 cycles and at the end of your treatment.

Quality of life
Everyone taking part in the study will be asked to complete 2 questionnaires

before you start treatment
after every 2 cycles of treatment
when you finish all the study treatment

These ask questions about how you are feeling and any side effects you have had. They are called quality of life questionnaires.

Tissue samples
To see what action the APR-246 is having on your cancer you have a sample of tissue taken (a biopsy) on the 2nd or 3rd day after having it. You might need to stay overnight after your biopsy.

You don't have to agree to this. You can still take part in the study.

Hospital visits

You see the doctors and have some tests before starting treatment. The tests might include:

blood tests
urine test
a physical examination
heart trace (ECG )
heart scan (echocardiogram ) or MUGA scan
a CT scan or MRI scan

Within 28 days of starting treatment, you have a sample of your tissue taken (a biopsy).

You go to hospital to have your treatment. You might need to stay overnight after having a biopsy. But usually your treatment will be as an outpatient.

You see the doctors regularly during treatment so they can see how you are. You have blood and urine tests. You might also have a repeat heart scan (echocardiogram) or MUGA scan.

You have a CT or MRI scan after every 2 cycles of treatment.

When you finish treatment on the study you see the doctors and have:

blood tests
a physical examination
heart trace (ECG )

You might also have a CT or MRI scan.

You see the doctors again 1 month later and then they might see you every 3 months. At these visits you have

a physical examination
blood tests
a CT or MRI scan

You might have a heart scan or MUGA.

Your doctor will tell you how often you are going to see them and what tests you might have.

Side effects

As APR-246 is a new drug there may be some side effects we don’t know about yet. You will be closely monitored during the time you have treatment and you will have a telephone number so you can contact the study nurse or doctor if you are worried about anything.

The most common side effects so far include:

dizziness
taste changes
headache
shaking (tremor)
feeling or being sick
diarrhoea
tiredness (fatigue)
a drop in white blood cells leading to an increased risk of infection
loss of appetite
a skin rash

You should tell your doctor if you take regular paracetamol or any medication that contains paracetamol. It is possible that if you take this at the same time as you have APR-246 it could temporarily affect how your liver works.

We have information on the side effects of