A trial of AZD4547 for breast cancer that is oestrogen receptor positive and has got worse despite having anastrozole or letrozole (RADICAL)

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 AZD4547 alongside anastrozole or letrozole to see if this treatment helps women with breast cancer that has got worse despite having hormone therapy. The researchers are looking at AZD4547 alongside anastrozole or letrozole. This trial is supported by Cancer Research UK.

If your breast cancer cells have oestrogen receptors, they are sensitive to the female hormone oestrogen (they are oestrogen receptor positive or ER positive).

Doctors can treat ER positive breast cancer with hormone therapy. Anastrozole and letrozole are drugs they often use. But sometimes, breast cancer stops responding to these drugs. Doctors describe this as becoming resistant.

If this happens, you may have another hormone therapy drug called exemestane. But researchers are looking for other ways to help women in this situation. In this trial, they are looking at a drug called AZD4547.

Growth factors are natural body chemicals that control cell growth. They work by binding to receptors, on cancer cells. This sends a signal to the inside of the cell, which sets off a chain of chemical reactions. AZD4547 is a type of biological therapy that works by blocking the receptor and stopping the signal from a growth factor called fibroblast growth factor (FGF). Drugs that block growth factor signals can stop cancer cells growing and dividing.

Also, if cancer cells have become resistant to letrozole or anastrozole, AZD4547 may make the cells more sensitive to these drugs and help them to start working again.

The trial is in 2 parts. In the 1st part, the researchers are looking for the best dose of AZD4547 to give at the same time as anastrozole or letrozole. In the 2nd part of the trial, they want to see if this treatment can shrink the cancer or stop it growing.

Who can enter

You may be able to enter this trial if you

  • Are a women who has breast cancer that is oestrogen receptor positive and has got worse despite having anastrozole or letrozole - you may have been having this on its own following surgery to try to stop your cancer coming back (adjuvant treatment), or as part of the first treatment you had after your cancer spread outside your breast
  • Are post menopausal (this means that you stopped having periods at least a year ago, or 2 years ago if you are under 50 or went through the menopause as a result of having chemotherapy)
  • Have at least 1 area of cancer that can be measured on a scan or X-ray
  • Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • Have satisfactory blood test results
  • Are at least 25 years old

If you join the 2nd part of the trial, you must have at least 1 area of cancer that is bigger than 10mm across and you must be willing to let the researchers have a sample of your breast cancer tissue. This is usually a sample of tissue that was removed when you were diagnosed. In rare cases where there isn't a stored sample available, you would need to have a new biopsy.

You cannot enter this trial if you

  • Have cancer that has spread to your brain or spinal cord, unless this has been successfully treated, is not causing any symptoms and you have not taken steroids for at least 4 weeks
  • Are under 25 years old
  • Have had more than 1 other hormone therapy drug for advanced breast cancer
  • Have already had a drug that blocks receptors for fibroblast growth factor (your doctors can advise you about this)
  • Have taken St John’s Wort in the last 3 weeks or any other drugs that affect body proteins called cytochrome P enzymes in the last 2 weeks
  • Have had major surgery in the last 4 weeks
  • Have had radiotherapy in the last 4 weeks or radiotherapy for symptoms in the last 2 weeks
  • Have not recovered from the side effects of any other cancer treatment unless they are very mild (apart from hair loss)
  • Have any problems with your digestive system that would make it difficult for you to swallow or absorb tablets
  • Have had another experimental treatment in the last 30 days (or earlier if there is any chance some of the drug could still be in your body)
  • Are known to be very sensitive to any of the drugs in the trial
  • Have had any other type of cancer in the last 5 years apart from non melanoma skin cancer or carcinoma in situ of the cervix that has been successfully treated
  • Have had laser treatment to your eyes, an eye condition called macular degeneration or certain other eye problems – the trial doctors can advise you about this
  • Have certain heart problems or another serious medical condition

You cannot enter the 1st part of the trial if you have had more than 1 type of chemotherapy for advanced breast cancer.

Trial design

This phase 1/2 trial is in 2 parts. In the 1st part of the trial, the researchers are looking for the best dose of AZD4547 that they can safely give at the same time as anastrozole or letrozole. The first few women taking part have the dose that is currently recommended by the company developing the drug. If they have any bad side effects, the next few women will have a lower dose. The aim is find a dose that you can have alongside anastrozole or letrozole without causing too many side effects.

The 2nd part of the trial will recruit 50 women. They will all have the best dose of AZD4547 that was found in part 1 (the dose may be different depending on whether you take anastrozole or letrozole).

When you join the trial, you carry on or restart taking anastrozole or letrozole tablets (you have whichever drug you have been taking before joining the trial). You have 4 week cycles of treatment. You have the study drug every other week, so in each treatment cycle

  • In the 1st week you have anastrozole or letrozole and you also have AZD4547 tablets twice a day
  • In the 2nd week you have anastrozole or letrozole alone
  • In the 3rd week you have anastrozole or letrozole and AZD4547
  • In the 4th week you have anastrozole or letrozole alone

As long as you don’t have any bad side effects, you can carry on having treatment for as long as it helps you.

Hospital visits

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

  • Physical examination including an eye test
  • CT scan or MRI scan or X-rays
  • Blood tests
  • Urine tests
  • Heart trace (ECG)
  • Heart ultrasound (echocardiogram) or MUGA scan

You then go to hospital

  • Once a week for the first 4 weeks of treatment
  • Twice in the following 4 weeks
  • Once a month after that

Everybody taking part will have regular blood tests. You have a CT scan or MRI scan in the 2nd cycle of treatment and then every 8 weeks.

You have an ECG every 4 weeks and an echocardiogram or MUGA scan in the 3rd cycle of treatment and then once every 3 months.

When you finish treatment, you see the trial team again and then go back and see them 4 weeks later.

Side effects

As AZD4547 is quite a new drug, there may be side effects we don’t know about yet. The common known side effects include

  • Constipation or diarrhoea
  • Dry or sore mouth
  • Hair loss
  • Dry skin
  • Changes to your nails
  • Feeling or being sick
  • Loss of appetite
  • Back pain or headache
  • Tiredness (fatigue)
  • Cough or shortness of breath
  • Dry eyes or other changes to your eyes which may affect your vision
  • Indigestion or stomach upset
  • High temperature (fever)
  • Increases in the levels of phosphates in the blood which may require medication to bring the levels back to normal

We have more information about the side effects of anastrozole, and letrozole.

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

Professor Michael Seckl

Supported by

AstraZeneca
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
Imperial College London
NIHR Clinical Research Network: Cancer

Other information

This is Cancer Research UK trial number CRUKD/11/004.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 5409

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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