“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”
A trial of chemotherapy with or without everolimus for HER2 breast cancer that has spread outside the breast (BOLERO 1)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
This trial is looking at chemotherapy and everolimus (Afinitor) for breast cancer that is HER2 positive and is locally advanced, or has spread to another part of the body (metastatic or secondary breast cancer). It is for women who have not yet had any treatment for advanced breast cancer.
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 (also known as Herceptin), which targets the HER2 protein.
You may have Herceptin with chemotherapy. Paclitaxel is one of the chemotherapy drugs commonly used.
Sometimes a drug can stop working, even though the cancer responded to it at first. Doctors call this
Everolimus is a drug that was first developed for people who have had a heart or kidney transplant. It helps to damp down the immune system to stop the body rejecting the new organ. But everolimus may also help to stop cancer cells growing.
The aim of this trial is to see if having everolimus at the same time as Herceptin and paclitaxel helps women with HER2 positive breast cancer that has spread outside the breast.
Who can enter
You can enter this trial if you
- Are a woman with breast cancer that is locally advanced or has spread and is HER2 positive
- Have areas of cancer that the trial doctors can measure
- Have satisfactory blood test results
- Are well enough to take part in the trial (performance status of 0 or 1)
- Are willing to use reliable contraception during the trial and for 4 weeks after if there is any chance you could become pregnant
- Are at least 18 years old
You cannot enter this trial if you
- Have cancer that your doctors think can be cured with surgery
- Have cancer that has spread to your brain
- Have already had treatment for breast cancer that is locally advanced or has spread – this does not include the treatment you had for early breast cancer unless the cancer came back less than a year after finishing Herceptin or chemotherapy
- Have a build up of fluid anywhere in the body such as the lungs (
pleural effusion) or abdomen ( ascites)
- Have had radiotherapy to more than a quarter of your
bone marrowin the last 4 weeks
- Already have symptoms of nerve damage, such as pins and needles or numbness in fingers or toes (peripheral neuropathy)
- Have already had any drug that works in a similar way to everolimus - the trial doctor can advise you about this
- Are known to be sensitive to any of the drugs in this trial
- Take drugs to prevent blood clots
- Have a
peptic ulceror any condition that could make it difficult for you to absorb tablets
- Have ever had a heart attack, or have other heart problems that are a cause for concern
- Have high blood pressure that cannot be controlled with medication
- Have an infection that cannot be controlled or any other medical condition that could affect you taking part in the trial
- Are pregnant or breastfeeding
- Are known to be HIV positive
This is an international study. It will recruit more than 700 people in different countries. It is a randomised trial. Everybody taking part will be put into 1 of 2 treatment groups by computer. Neither you nor your doctor will be able to choose a group, or know which group you are in. This is called a ‘
Everybody taking part will have Herceptin and paclitaxel. You have treatment on one day each week. Every 4 week period is called a cycle of treatment. In the first 3 weeks of each cycle, you have Herceptin and paclitaxel. In the 4th week, you have just Herceptin. You have both drugs through a drip into a vein. It takes about 2 hours each time.
- Women in group 1 also take everolimus tablets every day
- Women in group 2 take dummy tablets (
You take the tablets at the same time each day. You must not eat grapefruit, star fruit, pomegranate or Seville oranges (or drink their juices) during the trial. This is because they can affect the way everolimus works. And you can’t take some herbal medicines such as St John’s wort.
As long as you don’t have bad side effects, you can carry on having the treatment for as long as it helps you.
You will see the trial doctors and have some tests before you start treatment. The tests include
- Physical examination
- Blood and urine tests
- Heart trace (
- Tests to see how well your lungs are working (
lung function tests)
- Heart scan (
- CT scan
- Bone scan
- MRI scan
- X-rays of your bones
- Pregnancy test (if there is any chance you could become pregnant)
You go to hospital every week to have treatment. Every 8 weeks, you have a CT or MRI scan, a bone scan, and bone X-rays. And you have a MUGA scan or echocardiogram every 3 months.
When you finish treatment, you will go back to see the trial doctors within 4 weeks. After that, the trial team phone you to see how you are every 6 months for about 5 years.
If you stop having treatment for any reason other than your cancer getting worse, the trial team will ask you to carry on having scans until the cancer starts to grow again.
The possible side effects of everolimus include
- Sore mouth or mouth ulcers
- Tiredness (fatigue)
- Skin rash
- Diarrhoea or constipation
- Loss of appetite
- Swelling due to a build up of fluid (oedema)
- High temperatures (fever)
- A drop in the number of blood cells causing an increased risk of infection and bruising or bleeding problems
- High levels of cholesterol and sugar in the blood
If you have had hepatitis B in the past, this could become active again.
Rarely, everolimus can cause swelling (
The side effects of Herceptin and paclitaxel include
- Allergic reactions
- Fever and chills
- A drop in the number of blood cells causing an increased risk of infection, bruising or bleeding problems, tiredness and shortness of breath
- Heart changes
- Pain in muscles and joints
- Hair loss
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.
Dr Charles Swanton
NIHR Clinical Research Network: Cancer