A trial looking at giving bevacizumab (Avastin) with chemotherapy before surgery for early HER2 negative breast cancer (ARTemis)

This trial is comparing bevacizumab plus chemotherapy with chemotherapy only, before surgery for early stage breast cancer that is HER2 negative.

Often the first treatment for early breast cancer is surgery. We know from research that giving chemotherapy before surgery can help shrink the cancer. Shrinking the size of the cancer before surgery can mean you need a smaller operation.

Bevacizumab (Avastin) is a biological therapy called a monoclonal antibody. We know from research that bevacizumab can stop cancer growing by reducing its supply of oxygen and food. Doctors think that bevacizumab with chemotherapy may be better at shrinking cancer before surgery than chemotherapy on its own.

The aim of this trial is to find out if bevacizumab and chemotherapy together is better than chemotherapy only for shrinking breast cancer before surgery.

Recruitment

Start 01/04/2009

End 31/12/2012

Phase

Phase 3

Who can enter

You can enter this trial if you

Are a man or woman diagnosed with breast cancer
Have cancer in one or both breasts
Have breast cancer cells without HER2 receptors (HER2 negative breast cancer)
Have stage 2 or stage 3 breast cancer tumour that is bigger than 20mm across
Have breast cancer that is growing into your chest wall or skin (stage T4)
Have more than one area of cancer that in total adds up to more than 2 cm in size
Have inflammatory breast cancer
Have breast cancer tumours in the lymph nodes under your arm that add up to more than 20 mm in total or have 1 lymph node that is bigger than 20mm
Have satisfactory blood results
Are well enough to take part (performance status 0, 1, 2)
Are willing to use reliable contraception 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

Have a single breast lump less than 2cm across and no cancer spread to lymph nodes (stage 1 breast cancer)
Have breast cancer that has spread to another part of your body (stage 4 breast cancer)
Have breast cancer that has a large number of oestrogen receptors (ER positive)
Have had breast cancer before
Are not able to have chemotherapy before your surgery (your doctor will discuss this with you)
Are not able to have the drugs used in this trial
Have been treated for cancer before and it has not come back in the past 5 years, after being treated with surgery with or without radiotherapy or hormone therapy
Have had any other cancer except basal cell carcinoma, cervical carcinoma in situ or ductal carcinoma in situ (DCIS) of the same breast treated with surgery alone or DCIS treated with surgery with or without radiotherapy
Have had chemotherapy, radiotherapy or hormone therapy before
Have heart problems
Have high blood pressure that cannot be controlled with medication
Have had an ulcer before
Have bowel problems
Have kidney problems
Have an infection that is not controlled with medication
Have a wound that will not heal
Have a break or crack (fracture) in a bone
Have had major surgery, or injury, in the 28 days before agreeing to take part in the trial
Have any other serious medical condition that could affect you taking part in this trial

Trial design

This is a phase 3 trial. It will recruit about 800 people in the UK. It is a randomised trial. The people taking part are put into one of two groups by a computer. Neither you nor your doctor can choose which group you are put in.

In group 1 you will have docetaxel every 3 weeks for a total of 3 cycles; followed by 5-fluorouracil, epirubicin and cyclophosphamide (FEC) every 3 weeks for a total of 3 cycles.

People in group 2 will have the same as group 1 plus bevacizumab. You will have bevacizumab every 3 weeks for a total of 4 cycles. It starts at the same time as the docetaxel and ends with the first cycle of FEC. You will then have the last 2 cycles of FEC.

Each group has a total of 6 cycles of chemotherapy. You have all these drugs through a drip into a vein.

You will have your surgery to remove the cancer about 9 weeks after your chemotherapy ends.

The researchers may ask you to take part in up to 3 extra studies. You can choose whether you want to join any or all of them. Your choice will not affect you taking part in the main trial.

The first is a quality of life study. You fill in a questionnaire before you start chemotherapy and then again 2, 5, 8, 14 and 26 months after starting chemotherapy.

For the second study, the researchers would like 3 extra tissue samples (biopsies). They take these

Before you start your chemotherapy
After the 3rd cycle of docetaxel
After the 6th cycle of chemotherapy (This one may be taken when you have your surgery)

If you take part in the third study, the researchers would like to take up to 5 extra blood samples. These may be taken with your routine blood tests. You give these

Before you start chemotherapy
After the 1st cycle of chemotherapy
After the 2nd cycle of chemotherapy
After the 4th cycle of chemotherapy
Before you have surgery

The researchers will store all samples safely and anonymously, so no one will be able to link them to you. They will only be used for research purposes. Studying these samples may help researchers learn more about breast cancer.

If you don’t wish to give these extra samples for research, you don’t have to. You can still take part in the trial.

Hospital visits

You will see the doctor and have a number of tests before taking part in this trial. These tests include

Physical examination
Blood tests
Heart ultrasound (echocardiogram, or echo) or MUGA scan
Ultrasound scan
Biopsy
Urine test

If your doctor thinks you may need any other tests or scans they will discuss this with you.

Every 3 weeks during your treatment you will have

Blood tests
Urine test
Physical examination

Half way through your chemotherapy and at the end of it, you will have an ultrasound scan.

After your 4th cycle of treatment, you will have another heart ultrasound (echo) or MUGA scan.

You will have your surgery about 9 weeks after your chemotherapy ends. After surgery the trial doctor or one of the trial team will see you regularly for 10 years.

Side effects

All chemotherapy has side effects. The most common side effects of docetaxel, FEC and bevacizumab are

Fatigue
A drop in blood cells causing an increased risk of infection, bleeding and bruising
Constipation
Diarrhoea
Feeling or being sick
Sore mouth
Changes to taste
Loss of appetite
Hair loss
Skin rash
High blood pressure
Slow wound healing
Pain where the cancer is
Numbness and tingling in fingers and toes
Increased risk of blood clots
Heart problems
Kidney problems

You may have a reaction when you are having the bevacizumab, which can cause a skin rash, itching, breathlessness, coughing, feeling of swelling in the tongue or throat and a sore, itchy nose.

You can find more about docetaxel, FEC and bevacizumab on CancerHelp UK.