A study of tucatinib alongside capecitabine and trastuzumab for advanced breast cancer (HER2CLIMB)

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 study is looking at adding tucatinib to trastuzumab and capecitabine for people whose advanced breast cancer has continued to grow despite treatment. 

It is for people whose breast cancer is HER2 positive Open a glossary item. This means the breast cancer cells have tested positive for a protein called HER2.

More about this trial

Doctors often treat advanced HER2 positive breast cancer with trastuzumab (Herceptin). Trastuzumab is a type of targeted drug called a monoclonal antibody. It works by targeting and blocking the HER2 protein on the cancer cell. You might be treated with trastuzumab in combination with a chemotherapy drug called capecitabine. This is a standard treatment for HER2 positive advanced breast cancer. But it doesn’t always work. 
 
Doctors want to improve treatment for people with advanced breast cancer. In this study, they are looking at a new drug called tucatinib (also known as ONT-380). It is another type of targeted drug called a tyrosine kinase inhibitor. It works by targeting the HER2 protein but in a different way to trastuzumab.
 
Researchers think that adding tucatinib to capecitabine and trastuzumab might keep the cancer under control for longer. But they aren’t sure, so they want to find out more.
 
In this study, some people will have tucatinib, capecitabine and trastuzumab. And some will have capecitabine and trastuzumab.
 
The main aims of the study are to:
  • find out if tucatinib stops or delays the cancer growing better than trastuzumab and capecitabine alone
  • find out if tucatinib can improve how long people live for after treatment 
  • learn more about the side effects

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.
 
Who can take part
 
You may be able to join this study if all the following apply:
  • you have breast cancer that is HER2 Open a glossary item positive and the study team have tested a sample of tissue (biopsy) to confirm your HER2 status
  • you have breast cancer that has continued to grow into surrounding tissues (locally advanced cancer) and the doctors can’t remove it or it has spread elsewhere in the body after your last treatment to the whole body (systemic treatment Open a glossary item)
  • you have cancer that your doctor can see on a scan
  • you have cancer that has spread to the brain and has been treated, or doesn’t need treatment and is stable and you aren’t taking steroids unless you are on a stable dose
  • you have had treatment with trastuzumab, pertuzumab, and trastuzumab emtansine (TDM1)
  • your heart works well enough
  • you are willing to use reliable contraception during the study and for up to 7 months after the last dose of study treatment
  • 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 at least 18 years old

Who can’t take part
You cannot join this study if any of these apply.

Cancer related
You:
  • have cancer that has spread to the fluid in your brain or spinal cord and is causing symptoms
  • have had treatment with a drug called lapatinib within 12 months of starting study treatment, (except in some cases where lapatinib was given for no more than 21 days) or treatment with neratinib, afatinib or a similar drug in the past
  • have had capecitabine for cancer that has spread to other parts of the body (except in some cases where capecitabine was given for no more than 21 days)
  • have had the maximum life time dose of doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone or idarubicin - your doctor can confirm this
  • have had any anti cancer treatment such as chemotherapy, targeted cancer drugs or radiotherapy in the 3 weeks before starting study treatment
  • have side effects from past treatment unless they are mild, apart from hair loss or numbness and tingling in your hands or feet
  • have had any other cancer and you had treatment to the whole body within 2 years of starting the treatment in this study
Medical conditions
You:
  • have problems with your heart, such as a heart attack or angina that is not well controlled in the last 6 months, high blood pressure that is not well controlled, an abnormal rhythm of your heart or fluid around your heart (congestive heart failure)
  • take medication to thin your blood such as warfarin
  • can’t swallow tablets or you have a problem with your digestive system Open a glossary item that means you can’t absorb medication properly
  • take medication that affects body substances called CYP enzymes
  • have a condition called DPD (stands for dihydropyridine dehydrogenase which means you can’t break down some chemotherapy properly)
  • have hepatitis B or hepatitis C or liver disease that you have had for a long time (chronic liver disease)
  • have HIV
  • have any other serious medical condition, mental health or social problem 
Other
You:
  • are sensitive or allergic to trastuzumab, capecitabine, tucatinib or anything they contain unless they it was a mild reaction that was treated successfully
  • are pregnant or breastfeeding or planning a pregnancy
  • can’t have an MRI of the brain for any reason

Trial design

This phase 2 study is taking place in North America, Western Europe, Israel and Australia.
 
To begin with, the study team need to test a sample of tissue to check that your cancer cells are HER2 positive. They will test a sample that the doctors removed when you had a previous surgery or a biopsy Open a glossary item. They will ask you to give another sample if there isn’t a suitable sample available. Once they have confirmed this, you then have the other tests to check you are suitable to join this study.
 
It is a randomised study. You are put into 1 of 2 treatment groups by a computer. Neither you nor your doctor can decide which treatment group you are in. And neither of you will know which group you are in. This is called a double blind trial.
 
You are put into 1 of the following groups:
  • capecitabine, trastuzumab and tucatinib
  • capecitabine, trastuzumab and a dummy drug (placebo Open a glossary item)

Twice as many people will be in the group receiving tucatinib.

Tucatinib and the dummy drug are tablets. Capecitabine is a tablet. You have trastuzumab as a drip into a vein or as injection under the skin.
 
You have treatment in cycles. Each 21 day period is a cycle of treatment.
 
In each cycle, you:
  • take tucatinib or the dummy drug twice a day, everyday
  • take capecitabine twice a day, everyday starting on day 1 until day 14, followed by a week off
  • you have trastuzumab on day 1 
In some cases, you might have trastuzumab more often. Your doctor will tell you more if this applies.
 
You have treatment for as long as it is working and the side effects aren’t too bad.
 
Samples for research
The researchers will ask for a sample of your cancer (a biopsy Open a glossary item) that was removed when you had surgery or a biopsy. They will also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.
 
They plan to use the samples to look for:
  • biomarkers Open a glossary item to help predict who will benefit most from treatment 
  • what happens to tucatinib in your body (pharmacokinetics Open a glossary item)

Hospital visits

You see a doctor and have some tests before joining the study. These include:
  • physical examination
  • heart scan - ECHO (echocardiogram Open a glossary item) or MUGA Open a glossary item 
  • heart trace (ECG Open a glossary item)
  • blood tests
  • urine test
  • CT scan or MRI scan of your chest, tummy and the area between the hip bones (pelvis)
  • MRI scan of your brain
You have trastuzumab at the hospital every 3 weeks. You take capecitabine or the dummy tablets at home. On some hospital visit days, you take your tablets at the hospital. The study doctor or nurse will tell you when you need to do this. 
 
You also have some extra visits in the 1st and 2nd cycle of treatment.
 
At each hospital visit, you see the doctor for a check up and you have some blood tests. 
 
Every 6 weeks you have:
  • a CT scan or PET-CT scan of your chest, tummy and the area between the hip bones (pelvis)
  • an MRI of your brain if your cancer has spread to your brain
You have an ECHO (echocardiogram) or MUGA heart scan every 12 weeks. 
 
You stop having treatment if your cancer gets worse. A member of the study team will be in touch every 3 months to see how you are getting on. This might be at a routine hospital appointment or they might phone you. Your doctor will talk to you about other treatment options.

Side effects

The most common side effects of tucatinib are:
We have information about: 

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.

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

Chief Investigator

Professor Andrew Wardley

Supported by

Seattle Genetics Inc

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

15262

Print page
Questions to ask your doctor about clinical trials
Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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