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:
Status:
Phase:
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 . 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
The most common side effects of trastuzumab are
- Tummy pain
- Indigestion
- Feeling or being sick
- Loss of appetite
- Heart failure
- An allergic reaction causing fever and chills
You can find more information about TDM1, pertuzumab and trastuzumab in our cancer drugs section.
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
Professor Coleman
Supported by
Experimental Cancer Medicine Centre (ECMC)
Genentech Ltd
NIHR Clinical Research Network: Cancer
Roche
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
