A trial of everolimus and BEZ235 for advanced solid tumours

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

All cancer types

Status:

Closed

Phase:

Phase 1

This trial is looking at 2 drugs called everolimus and BEZ235 for advanced solid tumours Open a glossary item including breast cancer and kidney cancer. It is for people who have cancer that has spread to other parts of the body. A solid tumour is any type of cancer apart from leukaemia or lymphoma .

Everolimus is a type of biological therapy called an mTOR inhibitor. It stops a protein called mTOR from working properly. BEZ235 is a new drug that blocks the activity of mTOR and another protein called PI3K.

Both mTOR and PI3K are involved in cell growth. Blocking these 2 proteins may help stop cancer cells growing.

The aims of this trial are to

Find the highest doses of everolimus and BEZ235 that you can safely have together
Learn more about the side effects and what happens to the drugs in your body
See how these 2 drugs affect breast cancer and kidney cancer

Who can enter

This trial is in 2 parts. You may be able to enter the 1st part if you have a solid tumour Open a glossary item that can’t be removed with surgery or has spread to another part of your body. The cancer must also have got worse despite you having other treatment and there are no other standard treatments available for you.

If you have breast cancer, you may be able to enter the 2nd part of the trial if

Your breast cancer has spread to another part of your body
Your breast cancer is oestrogen receptor positive and HER2 negative
You have had at least 1(but no more than 2) types of chemotherapy for breast cancer that has spread
You have had at least 1 type of hormone therapy for breast cancer that has spread

If you have kidney cancer, you may be able to enter the 2nd part of the trial if

You have a type of kidney cancer called renal cell cancer that has spread to another part of your body
Your cancer has got worse despite having 1 (but no more than 2) drugs that target a receptor for a growth factor called VEGF (your doctor can advise you about this)

And as well as the above, for both parts of the trial you

Have cancer that is getting worse and can be seen and measured on a scan (or photographs if it is on your skin)
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Have satisfactory blood test results
Are at least 18 years old
Are willing to use reliable contraception during the trial and for 3 months afterwards if there is any chance you or your partner could become pregnant

You cannot enter either part of this trial if you

Have cancer that has spread to your brain or spinal cord unless it has been treated with surgery or radiotherapy, has not got any worse for at least 2 months, and you have not taken steroids for at least 1 month
Have already had everolimus or another drug that targets mTOR
Have had a drug called a PI3K inhibitor as part of another clinical trial
Have had any other experimental drug as part of a trial in the last 4 weeks
Have had radiotherapy or any other cancer treatment in the last 4 weeks, or have not recovered from side effects of earlier treatment (unless they are very mild)
Have taken steroids in the last 2 weeks unless you have been taking low dose steroids for a long time and the dose has not changed recently
Have had major surgery in the last 2 weeks, or earlier if you have not fully recovered or have a wound that has not healed
Have had a live vaccine in the last week
Have had another cancer in the last 3 years apart from carcinoma in situ of the cervix or non melanoma skin cancer
Have certain heart problems, an infection caused by a virus or any other medical condition that the trial team think could affect you taking part
Are known to be HIV positive
Are pregnant or breastfeeding

Trial design

This phase 1 trial will recruit about 73 people. The trial is in 2 parts.

In the 1st part of the trial, researchers are trying to find the highest doses of everolimus and BEZ235 that you can safely have together. This part of the trial is for people with different types of solid tumours. The first few people taking part will have low doses of both drugs. If they don’t have any serious side effects, the next few people will have higher doses. And so on, until they find the best doses to give. This is called a dose escalation study.

In the 2nd part of the study, the researchers want to learn more about side effects and see how the trial drugs affect kidney cancer or breast cancer that has spread. Everybody joining this part of the trial will have the highest safe doses of the drugs found in the 1st part of the trial.

You take everolimus and BEZ235 by mouth. You take BEZ235 twice a day and depending on when you join the trial, you take everolimus either once a day or once a week. Some people have everolimus alone for a week before starting BEZ235. The trial team will explain to you exactly how and when to take both drugs.

As long as you don’t have bad side effects, you can carry on taking the trial drugs for as long as they help you.

When you join the trial, the researchers will get a sample of your cancer that was removed in the past, when you had surgery or a biopsy Open a glossary item .

They will also ask you to have 2 more biopsies to look for substances called biomarkers Open a glossary item . Biomarkers are changes in genes and proteins that can help doctors to see how people respond to treatment. If you agree to this, the trial team will ask you to sign a separate consent form . But if you don’t want to take part in the biomarker study, you don’t have to. You can still take part in the main trial.

Hospital visits

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

Physical examination
Blood tests
Urine tests
Heart trace (ECG )
CT scan or MRI scan
Skin biopsy

You may also need to have a bone scan and a chest X-ray.

If there are abnormal areas on your skin that may be cancer, the trial team will take photographs. They may also take another biopsy from this part of your skin to check if it is cancer.

You go to hospital every week for the first 8 weeks of treatment, and then once every 4 weeks after that. For the first few people joining each part of the trial, there will be some extra hospital visits in the first 8 weeks.

You have blood tests at each visit, and 4 weeks after starting treatment you have another urine test, ECG and skin biopsy.

Some hospital visits may last quite a few hours because you have a number of blood tests before and after taking the trial drugs. The researchers use these blood samples to learn more about what happens to the drugs in your body. This is called pharmacokinetics Open a glossary item . It is possible that you may need to stay in hospital overnight on a couple of occasions.

You have a CT or MRI scan every 8 weeks during treatment and you may need to have more chest X-rays.

When you finish treatment, you have blood tests, urine tests an ECG and a CT or MRI scan (if you have not had one in the last 4 weeks). You may also have a chest X-ray.

You go back to see the trial team a month after finishing treatment. After that, a member of the team will phone to see how you are every 2 months until 5 years after the last person in the trial finishes their treatment.

If you stop the trial treatment for any reason other than your cancer getting worse, the trial team will ask you to have a scan every 8 weeks until you start another type of treatment.

Side effects

The common side effects of everolimus include

Sore mouth, mouth ulcers or dry mouth
Tiredness (fatigue)
Feeling or being sick
Skin reaction such as a rash or dry or itchy skin
Diarrhoea
Loss of appetite and weight loss
Tummy (abdominal) pain
Swelling of your legs or feet
Taste changes

The possible side effects of BEZ235 include

Fatigue
Diarrhoea
Feeling or being sick
Rash
Loss of appetite

The trial team will talk to you about other possible side effects of the drugs. We have more information about everolimus in our cancer drugs section.