A trial of TDM1 and pertuzumab for breast cancer that has spread - MARIANNE

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 3

This trial is looking at 2 new drugs called trastuzumab emtansine (TDM1) and pertuzumab for breast cancer that has spread to another part of the body (secondary breast cancer) or has come back in the same area (local recurrence). It is for people who have breast cancer that is HER2 positive.

Some breast cancers have large amounts of a protein called HER2 on the surface of the cells. These cancers are ‘HER2 positive’ and can be treated with a drug called trastuzumab which targets the HER2 protein.

You may have trastuzumab with chemotherapy. Paclitaxel and docetaxel are drugs that doctors often use.

Pertuzumab is a type of biological therapy called a monoclonal antibody. It works by targeting the HER2 protein but in a different way to trastuzumab. We know from research that having both pertuzumab and trastuzumab together may be better than having just one of them alone.

Trastuzumab emtansine (TDM1) is a combination of trastuzumab and a chemotherapy drug called DM1. Trastuzumab finds the cancer cells and delivers the DM1 to them. This type of drug is called a conjugated monoclonal antibody.

The researchers think that TDM1 alone, or in combination with pertuzumab may work well for people with HER2 positive breast cancer that has spread or come back in the same area. But they are not sure. In this trial, they will also compare it with a standard combination of trastuzumab and paclitaxel or docetaxel.

The aims of the trial are to find out which combination of drugs

Works best for breast cancer that has spread or come back in the same area
Is the safest

Who can enter

You may be able to enter this trial if you

Have breast cancer that has come back in the same area of the breast (local recurrence) or has spread to another part of the body and is HER2 positive
Have an area of cancer that can be seen on a scan
Are well enough to carry out your normal activities apart from heavy physical work (performance status 0, 1)
Have satisfactory blood test results
Are willing to use reliable contraception during treatment and for 6 months after if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Are able to have chemotherapy OR another standard treatment with the intent to cure your cancer
Have had any treatment for breast cancer that has spread or come back after treatment apart from hormone therapy
Have had paclitaxel, docetaxel or a chemotherapy drug from the vinca alkaloids group such as vincristine, vinblastine, vindesine or vinorelbine in the last 6 months
Have had hormone therapy in the last week
Have had trastuzumab or lapatinib in the last 3 weeks
Have already had TDM1 or pertuzumab
Have had an anti cancer drug as part of another clinical trial in the last 4 weeks
Have cancer that has spread to your brain that has not been treated and is growing, or has needed treatment to control symptoms in the last 2 months
Have had radiotherapy to the area of your body where your cancer has spread to in the last 2 weeks
Have had radiotherapy to about a third of your bone marrow (your doctor can advise you about this)
Have had bisphosphonates for symptoms of high levels of calcium in the last 3 weeks - you may join the trial if you take bisphosphonates for thinning of the bones (osteoporosis )
Have damage to your nerves (peripheral neuropathy ) that affects your daily activities
Have had the maximum life time dose of doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone or idarubicin - your doctor can confirm this
Are taking daily steroids
Are known to be sensitive to any of the drugs used in this trial
Have had another cancer in the last 5 years unless it has been successfully treated and your doctor does not expect it to come back
Have had a heart attack in the last 6 months
Have high blood pressure that is not controlled by medication
Have heart pain (angina) or a serious problem with the rhythm of your heart that is not well controlled
Have symptoms of heart failure
Become breathless while resting due to complications of your cancer or you require constant oxygen for any other reason
Have had major surgery in the last 4 weeks or may need it in the near future
Have had a major injury in the last 4 weeks
Are known to be HIV, hepatitis B or hepatitis C positive
Are pregnant or breastfeeding

Trial design

This is a phase 3 trial. It is an international trial and will recruit about 1,100 people from around the world. It is a randomised trial. You are put into 1 of 3 treatment groups by a computer. Neither you nor your doctor can choose which group you are in.

People in group 1 have trastuzumab and either paclitaxel or docetaxel. Your doctor can choose which chemotherapy drug is best for you.

People in group 2 have pertuzumab and TDM1.

People in group 3 have a dummy drug (placebo) and TDM1.

People in group 2 and 3 will not know if they are having pertuzumab or the dummy drug. This part of the trial is called a ‘blind trial’.

You have the drugs through a drip into a vein in 3 week cycles of treatment.

If you are in group 1, you have trastuzumab on day 1of each treatment cycle. If you have docetaxel, you have it on day 1 only. If you have paclitaxel you have it on days 1, 8 and 15.

People in groups 2 and 3 have TDM1 and pertuzumab (or the dummy drug) on day 1 of each 3 week treatment cycle.

Whichever group you are in, the treatment will take about 2 and half hours the first time you receive it. After this the treatment will take 1 hour. If you have a reaction during your treatment the nurses may slow it down or stop the drip for a short while. At the end of the first treatment, the nurses will observe you for about 1 to 2 hours to make sure you do not have a reaction to the drugs. And on your later treatments for about 30 minutes after.

As long as you don’t have bad side effects, you can continue to have the trial treatment for as long as it is helping you, or until your cancer starts to grow.

You will be asked to fill in a questionnaire on days 1 and 8 of the 1st and 2nd treatment cycle and then on day 1 of each cycle after that. It will ask you about how you have been and what side effects you have. This is called a quality of life questionnaire.

If you take part in this trial, the researchers will also ask your permission to take some extra blood samples and to get tissue samples from when you had a biopsy Open a glossary item . These samples will be stored safely and securely for future research. By studying these samples, the researchers hope to learn more about breast cancer and why some treatments work and some do not.

If you don’t wish to give these samples you don’t have to. You can still take part in the main trial.

Hospital visits

You will see the doctor and have some tests before starting treatment. These tests include

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

In the first 3 treatment cycles, everyone has a blood test on days 1, 8 and 15. In the other cycles, if you are having paclitaxel, you have a blood test on days 1, 8 and 15. Everyone else has a blood test just on day 1 of each cycle.

You have a MUGA or ECHO in cycle 1, cycle 3 and then every third cycle. You have a CT or MRI scan every 9 weeks for 81 weeks and then every 12 weeks until your cancer starts to grow.

About 4 to 6 weeks after stopping treatment you see the trial doctor and have

A physical examination
Blood tests
MUGA or ECHO
CT scan or MRI scan
Urine test

You then see the doctor every 3 months.

Side effects

TDM1 is a new drug and there may be side effects we don’t know about. The most common side effects reported are

Headache
Nose bleed
Sore, dry mouth
A drop in blood cells causing an increased risk of infection, bruising or bleeding
Difficulty breathing
Changes to your liver
Rash
Feeling or being sick
Diarrhoea
Constipation
Loss of appetite
Chest pain
Swelling of the arms and legs
Tingling, pain, numbness or pins and needles in your arms and legs
Bladder infection
Tiredness
Weight loss
Depression
Painful joints, muscles, back, arms and legs
A reaction to the drug causing flu like symptoms, fever, chills, shortness of breath, low blood pressure, wheezing, increased heart rate, hives and swelling of the throat

The most common side effects of pertuzumab are

A cough
Changes to your heart
A drop in blood cells causing an increased risk of infection, bruising and bleeding
Rash
Diarrhoea
Constipation
Loss of appetite
Feeling or being sick
Tummy and gut pain
Swelling of the arms and legs
Back pain
Sore joints
An allergic reaction causing fever, chills, low blood pressure and breathlessness
Tiredness