A trial looking at aromatase and COX 2 inhibitors before surgery for post menopausal early breast cancer (NEO EXCEL)

This trial is to find the best combination of aromatase and COX 2 inhibitors to shrink post menopausal breast cancer before surgery. The breast cancer must be sensitive to hormone therapy.

Doctors usually treat breast cancer with a combination of surgery, hormone therapy, radiation or chemotherapy. Having chemotherapy before surgery (‘neo adjuvant’) means the operation is smaller because the chemotherapy has already shrunk the cancer. But chemotherapy can have unpleasant side effects.

A hormone therapy called an aromatase inhibitor may give the same results as chemotherapy, with fewer side effects. If your breast cancer cells have oestrogen receptors (ER positive), the female hormone oestrogen can encourage breast cancer growth. After the menopause, your ovaries stop making oestrogen. But your adrenal glands still produce a small amount. Aromatase inhibitors stop the adrenal glands making oestrogen.

Researchers want to add the drug celecoxib to the aromatase inhibitor to see if this improves how well the treatment works. Celecoxib is a COX 2 inhibitor, which stops the cancer producing a survival enzyme called cyclo-oxygenase. The aims of this trial are to find out

Which aromatase inhibitor works best to shrink breast cancer before surgery
If aromatase inhibitors work better with or without a COX 2 inhibitor

Recruitment

Start 07/08/2007

End 01/05/2012

Phase

Phase 3

Who can enter

You can enter this trial if you

Have early invasive breast cancer
Have permanently stopped having periods (are ‘post menopausal’)
Have a breast cancer that has receptors for the hormone oestrogen (is ER positive)
Have breast cancer that measures at least 2cm across
Have not had treatment for breast cancer before
Have satisfactory blood test results
Are well enough to take part (performance status 0, 1 or 2)

You cannot enter this trial if you

Have cancer in both breasts (bilateral breast cancer)
Have cancer that has spread (metastasised) to other parts of your body
Have already had treatment for invasive breast cancer
Have had any other cancer except carcinoma in situ of the cervix or basal cell carcinoma that have been removed with surgery (resected)
Have another disease that would make it unsafe for you to have breast surgery or the trial treatment
Have another illness that could affect the results of the trial
Have a condition that could be made worse by celecoxib - you can check this with your doctor
Need ongoing treatment with regular non steroidal anti inflammatory or COX 2 inhibitor medication, apart from aspirin
Need ongoing treatment with fluconazole, ketoconazole, lithium or ‘ACE inhibitors’ (please note, you should never stop taking medication without talking to your doctor)
Are known to be allergic to celecoxib, exemestane, letrozole or a group of medicines called ‘sulphonamides’ - you can check this with your doctor
Have inflammatory bowel disease
Are taking medication to thin your blood (anti-coagulant therapy)

Trial design

This is a phase 3 trial, which will recruit 1,000 people. It is a randomised trial. The people taking part are put into 4 treatment groups by a computer. Neither you nor your doctor will be able to choose a group, or know which group you are in. This is called a ‘double blind’ trial.

Everyone in the trial will take an aromatase inhibitor, with celecoxib or a celecoxib ‘dummy’ tablet (a placebo).

If you are in group 1 you will have the aromatase inhibitor exemestane once a day, and celecoxib twice a day.

If you are in group 2 you will have exemestane once a day and a celecoxib dummy (placebo) tablet twice a day.

If you are in group 3 you will have the aromatase inhibitor letrozole once a day, and celecoxib twice a day.

If you are in group 4 you will have letrozole once a day and a celecoxib dummy (placebo) tablet twice a day.

All of the trial medication will be in tablet form. Everyone in the trial will take their medication every day for 16 weeks. You will then have your breast cancer surgery.

Hospital visits

Before you start the trial you will see the doctor and have some tests. These tests include

Physical examination
Breast ultrasound scan
Heart assessment (to check that you are fit enough for the trial medication)
Blood tests

When you start the trial, and 2 weeks later you will see the doctor and have some blood tests. You may also have a sample of your cancer removed to study in the laboratory (biopsy).

You will then see the doctor every month during the trial for a check up.

When you finish your treatment, you will see the doctor again and have some more tests. These tests include

Physical examination
Breast ultrasound scan
Taking a sample of your cancer (biopsy)
Blood tests

When you finish the trial treatment you will have your surgery within the next 2 weeks. You will then continue to see your regular doctors as you did before you started the trial.

The trial team will continue to collect information about your health after you have finished the trial. You will need to visit the hospital once a year for five years so that they can do this.