A trial of everolimus with letrozole for breast cancer that is oestrogen receptor positive and HER 2 negative (BOLERO 4)

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 a drug called everolimus (also called Afinitor) alongside a hormone therapy drug called letrozole for breast cancer. It is for women who have been through the menopause and who have breast cancer that

  • Has grown into tissue surrounding the breast or spread to another part of the body
  • Has receptors for the hormone oestrogen (hormone receptor positive)
  • Does not have receptors for a protein called HER2 (HER2 negative)

Doctors often treat this type of breast cancer with hormone therapy. Two drugs they can use are letrozole and exemestane. In this trial, researchers are looking at having a drug called everolimus alongside letrozole. The people taking part will be able to change to having exemestane with everolimus if their cancer gets worse.

Everolimus stops a protein called mTOR from working properly. Cells usually divide and grow in an orderly way. But in cancer cells, proteins such as mTOR can behave abnormally and the cells grow out of control. If mTOR is blocked, this may stop or slow the growth of the cancer.

The main aim of this trial is to see if the combination of everolimus and letrozole helps as a first treatment for post menopausal women with hormone receptor positive, HER2 negative breast cancer that has spread.

Who can enter

You may be able to join this trial if all of the following apply.

  • You have breast cancer that has grown into tissue surrounding the breast or spread to another part of your body
  • You haven’t had any other treatment for breast cancer that has spread and you can’t have surgery or radiotherapy to try to cure your cancer
  • Your cancer has receptors for the hormone oestrogen (hormone receptor positive) but doesn’t have receptors for the HER2 protein (HER2 negative)
  • You have been through the menopause
  • You have at least one area of cancer that can be measured on a scan and is at least 1cm across
  • You have satisfactory blood test results
  • You are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
  • You are at least 18 years old

You cannot join this trial if any of these apply. You

  • Have cancer that has spread to your brain or spinal cord (your central nervous system)
  • Have areas of cancer blocking the lymph vessels in both lungs (lymphangitic carcinomatosis)
  • Have already had hormone therapy for advanced cancer (you may have had hormone therapy before or after surgery to remove early stage breast cancer as long as you finished this treatment at least a year ago)
  • Have had radiotherapy in the last 4 weeks (or in the last 2 weeks if it was just to treat pain caused by cancer spread to the bone)
  • Have already had a drug called an mTOR inhibitor or are known to be very sensitive to this type of drug
  • Have had any other cancer in the last 5 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated
  • Are currently having hormone replacement therapy (HRT) unless you stop it before starting the trial treatment
  • Are having long term treatment with drugs that damp down your immune system
  • Take other medication that can affect body substances called cytochrome P enzymes in the 5 days before starting the trial treatment
  • Have problems with your blood not clotting normally
  • Are known to be HIV positive
  • Have any other medical condition that could affect your taking part (the trial doctors can advise you about this)

Trial design

This is a phase 2 trial. The trial team need 200 women to take part in different countries around the world. Everybody taking part will have everolimus and letrozole.

You take 2 everolimus tablets and 1 letrozole tablet every day. As long as you don't have bad side effects, you can carry on having this treatment for as long as it helps you.

If your cancer starts to get worse, the trial team will talk to you about changing from letrozole to exemestane. If you do this, you will take 2 everolimus tablets and 1 exemestane tablet every day. You can then carry on having this treatment for as long as it helps you.

Hospital visits

You see the trial team and have some tests before you start treatment. The tests include

  • Physical examination
  • Heart trace (ECG)
  • Blood tests
  • CT scan or MRI scan
  • Bone scan or X-rays of your bones (if you haven't had this done recently)

You may also have tests to see how well your lungs are working (lung function tests).

You see the trial team once every 4 weeks during treatment. Each visit lasts up to 2 hours. You have blood tests each time. You may need to have more heart traces (ECGs). You have a CT or MRI scan every 8 weeks.

When you finish treatment, you see the trial team again within 2 weeks. You have more blood tests, a CT or MRI scan and a bone scan.

The trial team will check how you are 4 weeks after you stop treatment. They may ask you to go to hospital for this. Or they may contact you by phone. A member of the trial team will then phone you every 3 months to see how you are and whether you've started any other treatment.

Side effects

This is the first time that everolimus and letrozole have been given together as a first treatment for breast cancer that has spread. So there may be some side effects we don't know about yet.

The most common side effects of everolimus include

The most common side effects of letrozole include

  • Changes in bone density that could lead to bones breaking
  • An increase in the amount of cholesterol in your blood (the trial team will check this regularly during the trial)

The most common side effects of exemestane include

  • Joint pain
  • Dizziness
  • Tiredness
  • Tummy ache, sickness or indigestion
  • Hot flushes
  • Muscle pain
  • Sweating

We have more 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.

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

Chief Investigator

Dr Mark Beresford

Supported by

Novartis

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 12151

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

Deborah wanted to help other breast cancer patients in the future

A picture of Deborah

“Deborah agreed to take part in a trial as she was keen to help other cancer patients in the future. "If taking part in a trial means others might be helped then I’m very happy with that."

Last reviewed:

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