A trial looking at trastuzumab and capecitabine with or without pertuzumab for advanced HER2 positive breast cancer - PHEREXA

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

Cancer type:

Breast cancer

Status:

Closed

Phase:

Phase 2

This trial is looking at adding a new drug called pertuzumab to trastuzumab (Herceptin) and capecitabine for women with breast cancer that has spread (secondary breast cancer). It is for women whose breast cancer is HER2 positive. This means the breast cancer cells have tested positive for a protein called HER2.

Doctors often treat HER2 positive breast cancer with trastuzumab. This is a type of biological therapy called a monoclonal antibody. It works by targeting and blocking the HER2 protein on the cancer cell.

Pertuzumab is a monoclonal antibody which also targets HER2 and works with trastuzumab in a complementary way.

We know from research that giving both these drugs together to women with HER2 positive breast cancer may be better than just giving one.

We also know from research that combining capecitabine with trastuzumab is better than capecitabine alone for women with HER2 positive breast cancer.

The aim of this trial is to find out if giving pertuzumab with trastuzumab and capecitabine is better than trastuzumab and capecitabine for women with HER2 positive breast cancer. And to find out more about the side effects of this combination of treatments.

Who can enter

You may be able to enter this trial if

You are a woman and have HER2 positive breast cancer that has spread to another part of your body
Your cancer has continued to grow while having trastuzumab
You have already had chemotherapy that included a taxane drug like paclitaxel or docetaxel
Your heart works well enough – your doctor will test for this
You have satisfactory blood results
You can take care of yourself (performance status 0,1)
You are willing to use reliable contraception during the trial and for 6 months after if there is a chance you could become pregnant
You are at least 18 years old

You cannot enter this trial if you

Have already had pertuzumab or capecitabine
Are having hormone therapy or immunotherapy
Have cancer that has spread to your brain or spinal cord (central nervous system) that is not well controlled – you may join the trial if you do not have any symptoms and are not taking steroids or anti cancer drugs
Have had more than the maximum acceptable dose of anthracycline chemotherapy – you can check this with your doctor
Have high blood pressure that is not controlled
Have a serious heart problem like congestive heart failure, angina that needs treatment, a problem with your heart rhythm or have had a heart attack in the last 6 months
Have had heart problems during, or after having trastuzumab before
Are known to be sensitive to any of the study drugs used in this trial
Have had chemotherapy in the last 3 weeks, radiotherapy in the last 4 weeks, major surgery or a major injury in the last 4 weeks and have not fully recovered
Have had another cancer in the last 5 years apart from carcinoma in situ of the cervix and non melanoma skin cancer
Need insulin to control diabetes
Have an infection and have been taking antibiotics in the last 2 weeks
Are known to be HIV, hepatitis B or hepatitis C positive
Are taking steroids daily – you may join the trial if you take inhaled steroids for asthma or a similar breathing condition
Have gut problems that affect the way you absorb tablets
Have another serious medical condition that could affect you taking part in this trial
Are pregnant or breastfeeding

Trial design

This is a phase 2 international trial. It aims to recruit 450 women from different countries around the world.

It is a randomised trial. You will be put into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in.

If you are in group 1 you have trastuzumab and capecitabine.

If you are in group 2 you have trastuzumab, capecitabine and pertuzumab.

Capecitabine is a tablet. You take the tablets twice a day for 2 weeks out of every 3. Your third week is a 7 day rest period when you do not take capecitabine. Each 3 week period is a cycle of treatment.

You have trastuzumab and pertuzumab as a drip in to a vein.

If you are in group 1 you have trastuzumab on day 1 of each cycle of treatment. The first time you have it over 90 minutes. You then stay for an hour to make sure you don’t have a reaction to it.

If you are in group 2 you have pertuzumab on day 1 and trastuzumab on day 2 of the first cycle of treatment. You have pertuzumab over 60 minutes. You then stay for another hour to make sure you don’t have a reaction to it. The following day you have trastuzumab over 90 minutes, with an hour of observation to make sure you don’t react. If you don’t have a reaction to either drug, you can have pertuzumab and trastuzumab on the same day for the rest of the treatment cycles.

If you have no problems with trastuzumab and pertuzumab, you can have these drugs over a shorter time with a shorter observation period after. If you react to either of them, they may be slowed down or stopped. If you stop either because of side effects, you may start that drug again when the side effect has gone.

If you need to permanently stop having trastuzumab or pertuzumab you can no longer take part in the trial and your doctor will discuss your treatment options with you.

If you need to permanently stop taking capecitabine you can continue to take part in the trial. If you are in group 1 you will continue with trastuzumab only. If you are in group 2 you will continue with trastuzumab and pertuzumab.

You continue having treatment as long as you don’t have bad side effects and it is still helping you.

The researchers will ask your permission to store some tissue samples from when you were first diagnosed. They will also ask to store some blood samples. By studying these samples they hope to learn more about how trastuzumab and pertuzumab works in the body and how it affects the body.

You don’t have to give permission for this if you don’t want to. You can still take part in the main trial.

Hospital visits

You will see the doctor and have some tests before taking part in this trial. These tests include

A physical examination
Blood tests
Urine test
Heart scan – ECHO or MUGA
Heart trace – ECG
CT scan or MRI scan
Bone scan

During treatment you see the doctor every 3 weeks for a physical examination and blood tests. You have a heart trace in cycle 1, 2 and 3. Then you have a heart trace and heart scan every 3 cycles until cycle 6 and then every 4 cycles. You have a CT scan or MRI scan every 9 weeks for 27 weeks then every 12 weeks until your cancer starts to grow again.

About 28 to 42 days after your last cycle of treatment you see the doctor and have

A physical examination
Blood tests
Urine test
Heart scan
Heart trace

You then see the doctor every 3 months.

Side effects

The most common side effects of pertuzumab are

Diarrhoea
A reaction to the drug causing fever, chills, low blood pressure, shortness of breath, headache, feeling or being sick
Rash

Common side effects of trastuzumab are

Diarrhoea
A reaction to the drug causing fever, chills, low blood pressure, shortness of breath, headache, feeling or being sick

A less common side effect of trastuzumab is that it can cause the heart not to pump as well as it should. Doctors call this heart failure. The symptoms of heart failure may include breathlessness, tiredness, swelling of the ankles or feet and constant coughing. Pertuzumab and capecitabine may also affect the way your heart works. Your doctor will check your heart regularly while you are having treatment. And if they are concerned they may stop your treatment for a short period of time or if necessary stop it completely.

The most common side effects of capecitabine are