A trial of TDM1 after surgery for breast cancer (KATHERINE)

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

Cancer type:

Breast cancer




Phase 3

This trial is comparing a drug called trastuzumab emtansine (TDM1) with trastuzumab (Herceptin), in people who had treatment to shrink their breast cancer before surgery, but still had some cancer remaining after this.

You may have treatment before breast cancer surgery to try to reduce the size of the cancer and make it easier to remove. This is called neoadjuvant treatment.

If you have a cancer with large amounts of a protein called HER2 Open a glossary item, doctors describe your cancer as HER2 positive. They can treat HER2 positive cancer with drugs such as trastuzumab, which targets the HER2 protein.

In this trial, researchers are looking at a drug called trastuzumab emtansine (TDM1), which is a combination of trastuzumab and a chemotherapy drug called DM1. They will compare it with trastuzumab.

The aim of this trial is to see if TDM1 is better than trastuzumab at stopping cancer coming back in people with HER2 positive breast cancer who still had some cancer remaining after neoadjuvant treatment.

Who can enter

You may be able to enter this trial if

  • You were diagnosed with breast cancer and had treatment to make it smaller before you had surgery to remove it
  • Your breast cancer cells test positive for the HER2 protein (the team will test for this again before you can take part)
  • You have had at least 6 cycles of systemic treatment Open a glossary item to shrink your cancer before surgery, this lasted for at least 16 weeks and included at least 9 weeks of both trastuzumab and a taxane drug Open a glossary item (these could have been at the same time)
  • You still had some cancer remaining after this treatment
  • The pathologist Open a glossary item examined the tissue removed during your breast surgery and could see that your surgeon had been able to remove all the cancer in your breast and lymph nodes Open a glossary item - if you have remaining cancer cells in your breast or lymph nodes and these are removed with further surgery, you may also be able to take part
  • Your surgery was less than 12 weeks ago
  • You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • You have satisfactory blood test results
  • You are willing to use reliable contraception during the trial and for 7 months afterwards if there is any chance that you or your partner could become pregnant
  • You are at least 18 years old

You cannot enter this trial if

  • Your cancer has spread to another part of your body or was very small in size when it was diagnosed and had not spread to any of your lymph nodes – you can check this with your doctor
  • You have had another breast cancer in the past (if you had a type of pre breast cancer called lobular carcinoma in situ you may still be able to take part)
  • Your cancer continued to grow during your neoadjuvant treatment or your surgeon was not able to remove all the cancer or your cancer has come back after surgery
  • You have had an anti cancer drug treatment in the last 28 days
  • You have had more than a certain amount of anthracycline chemotherapy Open a glossary item, such as doxorubicin or epirubicin – you can ask your doctor about this
  • Your doctor would usually recommend radiotherapy for your situation, but you cannot have this for medical reasons
  • You have had any other cancer in the last 5 years apart from successfully treated carcinoma in situ of the cervix or non melanoma skin cancer, stage 1 womb cancer or any other very early cancer Open a glossary item - you can ask your doctor about this
  • You have moderate to severe numbness and tingling in your hands and feet Open a glossary item
  • You have a serious heart problem
  • You have already had treatment with TDM1
  • You have an infection that can’t be controlled with medication
  • You have HIV
  • You have hepatitis B, hepatitis C or another disease affecting your liver
  • You have another medical condition apart from your cancer that can’t be controlled with medication or is a cause for concern
  • You have had major surgery in the last 28 days, or you would be due to have surgery for another condition while you are on the trial
  • You are allergic to trastuzumab or any other drugs that contain mouse protein – you can ask your doctor about this
  • You are pregnant or breastfeeding

Trial design

This phase 3 trial will recruit 1484 people all over the world. About 58 people will take part in the UK. The trial is randomised. The people taking part will be put into 1 of 2 groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

If you are in group 1, you have TDM1 every 3 weeks, through a drip into a vein. Each 3 week period is called a cycle of treatment.

If you are in group 2, you have trastuzumab every 3 weeks. You have trastuzumab through a drip into a vein.


As long as you are coping with any side effects, you can have up to 14 cycles of treatment.

As well as the trial drug, you will also have radiotherapy or hormone therapy if your doctor thinks you need them. This is standard treatment Open a glossary item, and not part of the trial.

The trial team will ask you to fill out a questionnaire before you start treatment and at weeks 13 and 31. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Before you joined the trial, the team will have tested a sample of your breast tissue removed during surgery, to see if it has large amounts of the protein HER2. They would like to use this sample to do other tests.

The team will talk to you about this before you agree to join the trial. If you do not want to have these tests done on this tissue sample, you will not be able to take part.

Hospital visits

Before you start treatment, you see the doctor and have some tests. These tests include

  • Physical examination
  • Heart trace (ECG) Open a glossary item
  • Heart scans (echocardiogram Open a glossary item or MUGA scan Open a glossary item)
  • X-ray of your breast (mammogram) if you have not had one in the last year
  • Blood tests

You see the team once every 3 weeks for as long as you have treatment. Then for the rest of the year you

  • Have blood tests every 3 months
  • Fill out a quality of life questionnaire every 6 months

In the next 2 years, you have

  • A physical examination every 3 months
  • An ECHO or MUGA scan at 3, 6, 12, 18 and 24 months
  • A mammogram each year

For 2 years after that, you

  • Have a physical examination every 6 months and a mammogram each year
  • Fill out a quality of life study at 3 years
  • Have an ECHO or MUGA scan at 3, 4 and 5 years

From the 6th year until the10th year after you started the trial, you have a physical examination and a mammogram each year.

The team will pay for your travel costs and snacks when you are at the hospital.

Side effects

Side effects of TDM1 include

  • A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
  • Numbness and tingling in your hands and feet (peripheral neuropathy)
  • Shortness of breath
  • Tiredness (fatigue)
  • Cough
  • Swelling in the lungs or a blood clot in the lungs (these are rare)
  • Changes to the way your liver or heart works
  • Difficulty sleeping
  • Dry and sore mouth
  • Low levels of potassium in your blood
  • Taste changes
  • Eye discomfort – redness, dryness, blurred vision, or an increase in the amount of tears you produce
  • High blood pressure
  • Dizziness
  • A reaction to the drug causing flu like symptoms, fever, chills, shortness of breath, low blood pressure, rash, throat swelling and fast pulse
  • Feeling or being sick
  • Diarrhoea
  • Constipation
  • Tummy pain
  • Joint and muscle pain
  • Swelling under the skin of your arms and legs, caused by a build up of fluid (oedema)
  • Weakness
  • Headache
  • Nose bleeds
  • Skin rash

Common side effects of trastuzumab include

  • A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
  • Dizziness
  • Problems sleeping
  • Watery, red or swollen eyes
  • Cold and flu like symptoms
  • Nose bleed
  • Sore mouth
  • Shortness of breath
  • Skin rash or flushing
  • Cracked nails
  • Hair loss
  • Tenderness, pain, reddening, tingling or a burning feeling in your hands or feet
  • Feeling or being sick
  • Constipation
  • Diarrhoea
  • Heartburn and indigestion
  • Loss of appetite and taste
  • Weight changes
  • Pins and needles or numbness of the skin
  • Painful joints, muscles, chest, throat and tummy
  • Tiredness and weakness
  • Fever, chills and headache
  • Swelling caused by a build up of fluid in your tissues – this may affect any part of your body

You will be exposed to extra radiation from having a mammogram each year for the trial, as well as regular MUGA scans. But the team think that any risk to you would be minimal.

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Andrew Wardley

Supported by

Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 10447

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Harriet wanted to try new treatments

A picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

Last reviewed:

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