A study of ceralasertib for advanced cancer (Dose expansion study)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
This study is looking at ceralasertib (AZD6738) for solid cancers that have spread to another part of the body. A
There are 2 parts to this study. This summary is about the dose expansion study. We have another summary about the dose escalation study.
More about this trial
Ceralasertib is a new drug. It works by stopping a protein called ATR. A change (
Researchers think ceralasertib combined with other anti cancer drugs might work well to stop cancer growing.
First they need to find the best dose of ceralasertib to give by itself and in combination with the other drugs. This is the dose escalation study. After completing this the team will do a dose expansion study.
The aim of the dose expansion study is to find how well ceralasertib in combination with other anti cancer drugs works to stop cancer growing.
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 the study if you are in one of the following situations.
You have
Or
You have non small cell cancer (NSCLC) that is an
- Your cancer has spread into the surrounding tissue (locally advanced) or has spread to another part of the body
- You have had at least 1 course of treatment with chemotherapy that included a
platinum chemotherapy drug such as carboplatin - There is no further standard treatment
- You have at least 1 area of cancer that measures 10mm or more across (15mm or more for a
lymph node ) that can be seen on a scan and hasn’t been treated with radiotherapy
Or
You have stomach cancer or cancer of the
- Your cancer has spread into the surrounding tissue (locally advanced) or has spread to another part of the body
- Your cancer cells have a low amount of the ATM protein. The doctors will check for this.
- Your cancer has come back after or continued to grow during your first course of chemotherapy treatment (
first line treatment ) - Your chemotherapy included 5FU and a platinum drug such as carboplatin or cisplatin
- There is no further standard treatment
- You have at least 1 area of cancer that measures 10mm or more across (15mm or more for a lymph node) that can be seen on a scan and hasn’t be treated with radiotherapy
Or
You have breast cancer that is
Or
You have high grade epithelial ovarian cancer or fallopian tube cancer or primary peritoneal cancer and:
- You have or might have the BRCA or RAD51CD gene change
- You have had chemotherapy that included a platinum drug and your cancer had not got worse within 6 months of finishing treatment
- You must have had treatment with a drug called a
PARP inhibitor , for example olaparib. for 6 months or a year after your initial chemotherapy - If you had olaparib you didn't stop taking it due to the side effects
- If you had another PARP inhibitor you must have stopped taking it at least 14 days before starting treatment
And all of the following apply, you:
- Have satisfactory blood test results
- Are fully active but can’t do heavy physical work (performance status 0 or 1) and this hasn’t got worse in the past 2 weeks
- Are willing to use reliable contraception during treatment and for at least 6 months afterwards if there is any chance you or your partner could become pregnant
- Are at least 18 years old
You cannot join this study if any of these apply.
Cancer related
- You have NSCLC that has the gene change (
mutation ) EML4-ALK or a mutation of the epidermal growth factor receptor (EGFR) - Your cancer is pressing against your spinal cord (
spinal cord compression ) - Your cancer has spread to the brain unless you have no symptoms, it is stable and you have not been taking steroids for at least 4 weeks before starting treatment in this study
- You have had any anti cancer drug treatment in the past 4 weeks
- You have had olaparib, or a similar drug before
- You have had radiotherapy within 4 weeks of starting treatment, 1 week if it was a small area to relieve symptoms apart from radiotherapy to more than 30% of the
bone marrow - You have ongoing side effects from previous treatment apart from hair loss
- You have had steroids within the 4 weeks before starting treatment
- You have had an experimental drug as part of a clinical trial within 4 weeks of starting treatment
- You have had another cancer in the past 5 years apart from successfully treated
in situ carcinoma of the cervix, treatednon melanoma skin cancer , ductal carcinoma in situ (DCIS ), early womb cancer or anothersolid cancer including somelymphomas that have been successfully treated and there hasn't been any sign of it for the past 5 years or more
Medical conditions
- You have a condition called ataxia telangiectasia
- You have had a heart attack in the past 6 months or another heart problem such as heart failure, unstable angina or unstable heart rhythm
- You have high blood pressure that isn’t controlled by medication
- You have a problem with your
digestive system such as Crohn’s disease or IBS that could affect how ceralasertib is absorbed - You have fits (seizures) that can’t be controlled with medication
- You have an infection that needs to be treated with drugs such as antibiotics that reach your whole body (
systemic treatment ) - You have HIV, hepatitis B or hepatitis C
- You have any other medical or mental health condition that the team think could affect you taking part in the study
Other
- You are taking any medication that affects the CYP enzymes or the Pgp protein
- You have had ceralasertib or any drug that works in the same way
- You are allergic to ceralasertib or any of its ingredients
- You are pregnant or breastfeeding
There are different parts to the study and you might not be able to join a certain part if any of the following also apply. You:
- Are not able to have carboplatin
- Have or might have myelodysplastic syndrome (MDS)
- Have or might have acute myeloid leukaemia (AML)
- Have had a
biological therapy as part of a clinical trial in the past 7 weeks - Have had a blood transfusion in the past 4 months
- Have a blockage of the gut
- Have severe bleeding of the food pipe (oesophagus) or stomach within the 4 weeks of starting treatment
- Are allergic to olaparib or any of its ingredients
- Are allergic to durvalumab or any of its ingredients
- Have had medication that affects the
immune system such as steroids within 4 weeks - Have had a
live vaccine within a month of starting treatment - Have or have had
sarcoidosis - Have or have had
tuberculosis
Trial design
There are separate parts to this study. Which part you are in will depend on your cancer type and when you join.
This is a phase 1 study. The study team need about 156 people in total to take part.
In the dose escalation study researchers found the best dose of ceralasertib to give with:
In the dose expansion study the doctors use these combinations to treat people with certain cancers. So if you have:
- non small cell lung cancer you have carboplatin and ceralasertib
- squamous cell head and neck cancer you have durvalumab and ceralasertib
- adenocarcinoma of the stomach or gastro-oesophageal junction you have olaparib and ceralasertib
Ceralasertib is a tablet. You take it on an empty stomach. You can’t eat or drink anything apart from water for 2 hours before, or an hour after, taking your tablets. Your doctor will tell you how many to take.
You have carboplatin as a drip into a vein every 3 or 4 weeks. You have 6 treatments.
Olaparib is a tablet. Your doctor will tell you when to take them and how many. You continue having olaparib and ceralasertib as long as it is helping you and the side effects aren’t too bad.
You have durvalumab as a drip into a vein every 6 weeks. You continue having durvalumab and ceralasertib as long as it is helping you and the side effects aren’t too bad.
Samples
The researchers will ask for samples of tissue (
You have some additional blood tests as part of this study. These are to measure specific substances in the blood (
You will be asked if you’re willing to have an extra blood test. This is for genetic research. You do not have to give this sample if you don’t want to. You can still take part in the main study.
The researchers use all these samples to find out more about cancer and how ceralasertib works.
Hospital visits
You see the doctor and have some tests before taking part. These tests include:
During treatment you see the doctor regularly and have the same tests. How often you have them depends on which treatment you are having.
A month after finishing treatment you see the doctor and have the same tests.
You then see the doctor every 6 to 8 weeks until your cancer starts to grow again.
Side effects
Ceralasertib is a new drug. This is the first time it is being used in humans and there may be side effects we don’t know about yet. Side effects of ceralasertib might include:
- a change to the way the heart and liver works
- inflammation of the
digestive system - bleeding from the digestive system
- a drop in the number of blood cells causing an increased risk of infection, bruising and bleeding
- feeling or being sick
- high blood pressure
- an increase in your skin's sensitivity to sunlight
You are monitored very closely while taking ceralasertib. Tell your doctor or nurse if your general health changes while taking ceralasertib.
We have information on the side effects of:
Your doctor will talk to you about the side effects before you agree to take part.
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 Matthew Krebs
Supported by
AstraZeneca
Experimental Cancer Medicine Centre (ECMC)
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040