A trial of ipatasertib, paclitaxel and atezolizumab for breast cancer

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

Cancer type:

Breast cancer

Secondary cancers

Status:

Closed

Phase:

Phase 3

This trial is looking at ipatasertib, paclitaxel and atezolizumab for breast cancer that has spread to another part of the body (advanced breast cancer).

It is for people with advanced breast cancer that has:

no receptors for the hormones oestrogen and progesterone or the protein HER2 (triple negative breast cancer) OR
receptors for the hormones oestrogen and, or progesterone and there are none or few receptors for the HER2 protein (hormone positive/HER2 negative breast cancer)

More about this trial

When you agree to take part in this trial the team will ask for a small piece of cancer tissue from when you were first diagnosed. They test this to see if your cancer has certain gene changes. Which treatment you have in the trial depends on whether your cancer has these gene changes or not.

If your cancer doesn’t have any of the certain gene changes you can’t continue to have treatment in this trial. In this case, your doctor will talk to you about what is the best treatment for you.

Ipatasertib is a targeted cancer drug called a growth blocker. It works by blocking a protein called Akt that is known to help cancer cells grow. Changes (mutations) in certain genes affect how the Akt protein works.

Paclitaxel is a chemotherapy drug used for breast cancer.

Early studies suggest that combining ipatasertib with paclitaxel might improve how well the treatment works.

In this trial you will have one of the following:

ipatasertib and paclitaxel
paclitaxel and a dummy drug (placebo)

Atezolizumab is a type of immunotherapy. It blocks a protein called PD-L1. This triggers the immune system to attack and kill cancer cells.

Early studies suggest that adding atezolizumab to ipatasertib and paclitaxel might work for advanced triple negative breast cancer.

If you have triple negative breast cancer and it doesn’t have at least 1 of the gene changes that affect the Akt protein you will have ipatasertib, paclitaxel and atezolizumab.

The researchers want to find out:

how well the combination of ipatasertib and paclitaxel works
how well the combination of ipatasertib, paclitaxel and atezolizumab works for triple negative breast cancer
more about the side effects of these treatments

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 enter
You may be able to join this trial if your cancer is one of the following, it has:

no receptors for the hormones oestrogen and progesterone or the protein HER2 (triple negative breast cancer)
receptors for the hormones oestrogen and, or progesterone and there are none or few receptors for the HER2 protein (hormone positive/HER2 negative breast cancer)

And all of the following apply:

your cancer has spread into the nearby tissue (locally advanced) or to another part of the body (metastatic)
tests on tissue from your cancer shows certain gene changes
your cancer can be measured
you have satisfactory blood test results
you are able to do everything apart from heavy physical work (performance status 0 or 1)
you are willing to use reliable contraception during treatment and for a month after ipatasertib and 6 months after paclitaxel
you are at least 18 years old

Who can't take part
You cannot join this trial if any of these apply.

Cancer related
You:

have cancer that has spread to your brain or spinal cord
have already had chemotherapy for your advanced breast cancer
are able to have hormone therapy drugs, such as tamoxifen or letrozole, for your hormone positive/HER2 negative breast cancer
have on going side effects from any treatment apart from hair loss and mild nerve damage (peripheral neuropathy)
have had radiotherapy to relieve symptoms, such as bone pain, (palliative radiotherapy) unless it was 2 weeks ago and you have no side effects from the treatment
have pain caused by your cancer that isn’t controlled
have low amounts of calcium in your body or have symptoms of a low amount of calcium and need to have treatment with a bisphosphate drug. You might be able to take part if you need bisphosphate treatment to prevent cancer spreading to the bones or osteoporosis and you don’t have a history of very low levels of calcium
have had another cancer in the past 5 years apart from successfully treated, in situ cancer of the cervix, non melanoma skin cancer and stage 1 womb cancer
have had another cancer treatment in the past month

Medical conditions
You have:

a problem with your digestive system that affects how you absorb food, drink and medication
HIV, hepatis B or hepatitis C
type 1 or 2 diabetes and you need insulin to control your diabetes
cirrhosis or history of severe liver disease
had a heart attack or unstable angina in the past 6 months
another major heart problem such as heart failure, you take medication to control an irregular heart beat or an abnormal heart trace (ECG)
had major surgery in the past month or haven’t recovered from surgery
had a major injury in the past month
another medical or mental condition that your doctor or the trial team think will affect you taking part

Other
You are:

not able to or not willing to take tablets
pregnant or breastfeeding

Trial design

This is a phase 3 trial. There are 2 groups in this trial.

Group A

This group is for people with breast cancer with receptors for hormones oestrogen and, or progesterone and none or few receptors for the HER2 protein (hormone positive/HER2 negative breast cancer).

The researchers need 450 people to join.

It is a randomised trial. You are put into 1 of 2 treatment groups. Neither you or your doctor can choose which group you are in. And neither you or your doctor will know which group you are in. It is a double blinded trial.

The 2 groups are:

ipatasertib and paclitaxel
paclitaxel and a dummy drug (placebo)

2 out of every 3 people are put into the ipatasertib and paclitaxel group.

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You have treatment in 4 week periods called treatment cycles.

Ipatasertib and the dummy drug are tablets. You take 2 tablets every day for 3 weeks then you have a week off.

You have paclitaxel as a drip into a vein. You have it once a week for 3 weeks then have a week off. The drip takes an hour.

This is one cycle of treatment. You then start the next cycle of treatment.

You continue having treatment as long as it is helping you and the side effects aren't too bad.

Group B

This group is for people with breast cancer that has no receptors for the hormones oestrogen and progesterone or the protein HER2 (triple negative breast cancer) and no gene changes.

In this group the researchers need 100 people to join. Everyone has ipatasertib, atezolizumab and paclitaxel.

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You have treatment in 4 week periods called treatment cycles.

Ipatasertib and the dummy drug are tablets. You take 2 tablets everyday for 3 weeks and then have a week off.

You have atezolizumab as a drip into a vein. You have it once a week for 2 weeks and then have 2 weeks off. The drip takes between 30 minutes and 60 minutes.

You have paclitaxel as a drip into a vein. You have it once a week for 3 weeks then have a week off. The drip takes an hour.

This is one cycle of treatment. You then start the next cycle of treatment.

You continue having treatment as long as it is helping you and the side effects aren't too bad.

Information about paclitaxel and ipatasertib

Paclitaxel can cause an allergic reaction. To prevent this, you have some medication to take at home 12 hours and 6 hours beforehand. This is pre medication. Your doctor or nurse will tell you about this.

Ipatasertib and paclitaxel can cause diarrhoea. You might be given some anti diarrhoea tablets to take home. If you do have diarrhoea after treatment:

take the tablets as your doctor or nurse tells you to
drink plenty of fluid
tell your doctor or nurse

Patient diary
You have a patient diary to write down:

when you had your tablets
any other medication you have taken
any side effects

Quality of life
You fill in a couple of questionnaires:

before starting treatment
every 4 weeks while having treatment
4 weeks after completing treatment
every 3 months until your cancer starts to grow again

The questions will ask about:

side effects
how you are feeling
what you can do
your general health

Blood and tissues samples
You will have regular blood tests to monitor your safety. For some samples you cannot eat or drink, apart from water, for 8 hours before having the blood sample taken. Your doctor or nurse will tell beforehand when you’re going to have these tests.

They will use these blood samples to look for substances (biomarkers) in your blood. These biomarkers might help them better understand this type of breast cancer. And to find out what happens to ipatasertib in your body.

The team will ask for a small piece of cancer tissue from when you were first diagnosed. They will use this to find out if your cancer has the changes in the genes that affect the Akt protein. They will ask for an new sample (biopsy) if this isn’t available.

They will use any remaining tissue to help them understand this type of breast cancer better.

Other information
During treatment and for 10 days after finishing treatment you can’t:

have grapefruit juice
take certain medications including over the counter medications, such as St John’s Wort
have a live vaccine

Your doctor will talk to you more about this including medications you can and can’t have.

Hospital visits

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

a physical examination
blood tests
urine sample
heart trace (ECG)
heart scan (ECHO or MUGA)
bone scan
CT scan or MRI scan

During treatment you see the doctor every week for a physical examination and to see how you are.

You see the doctor a month after finishing treatment for some of the same tests you had before the start of treatment.

About every 3 months after treatment you see the doctor or a member of the trial team will phone you to:

see how you are
ask if you have had any other cancer treatment

You have a CT scan or MRI scan every 8 weeks until your cancer starts to grow again.

Side effects

Your doctor and nurse will monitor you closely for any side effects. Let your doctor or nurse know as soon as possible if:

you have a change in your condition
you become ill
you have any side effects
your side effects aren’t getting any better
your side effects are getting worse

Early treatment can help manage side effects better, especially diarrhoea and sickness.

Ipatasertib is a new drug. There may be side effects we don’t know about when it is used by itself or in combination with other drugs.

The most common side effects reported so far include:

diarrhoea
feeling or being sick
feeling tired (fatigue)
feeling weak
rash including redness of the skin that might be itchy or not
high levels of sugar in the blood
sore mouth or ulcers

The most common side effects of atezilozumab include:

feeling tired
lack of energy
loss of appetite
diarrhoea
stomach (abdominal) pain
shortness of breath
headache
itching
feeling or being sick
high temperature (fever)
muscle and bone pain

Atezilozumab increases the number of immune cells in your cancer tissue and healthy tissue. This can cause inflammation. The inflammation in the healthy tissue migth cause an autoimmune condition.

We have information about the side effects of paclitaxel.

Your doctor will talk to you about the possible side effects of the drugs used in this trial before you agree to take part.