A trial of LDE225 with gemcitabine for advanced pancreatic cancer

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

Cancer type:

Pancreatic cancer

Status:

Closed

Phase:

Phase 1

This trial is looking at a drug called LDE225 alongside gemcitabine chemotherapy for cancer of the pancreas that has spread.

If pancreatic cancer has spread outside the pancreas, it is called advanced pancreatic cancer. Doctors may treat advanced pancreatic cancer with chemotherapy. Gemcitabine is a drug they often use.

Researchers are looking for ways to improve treatment for advanced pancreatic cancer and in this trial they are looking at a drug called LDE225.

Cells normally grow in a very orderly way. Chemical messages or signals tell them when to grow and when to stop. But in cancer cells the normal signalling system changes. So the cells keep on dividing and the cancer grows.

LDE225 can block a type of cell signalling called the hedgehog pathway. We know from research that the hedgehog pathway can affect the growth of several types of cancer including cancer of the pancreas.

In this trial, researchers want to see if having LDE225 with gemcitabine can help people with pancreatic cancer that has spread. The main aims of the trial are to

Find the highest safe dose of LDE225 you can have alongside gemcitabine
Learn more about the side effects of having both drugs together and what happens to LDE225 in the body

Who can enter

You may be able to enter this trial if you have adenocarcinoma of the pancreas that has spread into surrounding tissues or to another part of your body and cannot be removed with surgery.

You must not have had any other treatment for pancreatic cancer apart from the following.

For the 1st part of the trial, you may have had chemotherapy (other than gemcitabine) and your cancer got worse despite having this treatment. Or, you may have had gemcitabine after surgery to stop the cancer coming back as long as you had this treatment more than a year ago.

For the 2nd part of the trial, you may have had gemcitabine after surgery to stop the cancer coming back, as long as you had it more than a year ago. But you must not have had any other chemotherapy drugs.

As well as the above, for both parts of the trial, you must

Have satisfactory blood test results
Be well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
Be willing to use reliable contraception during the trial and for 4 months afterwards (for women) or 6 months (for men) if there is any chance you or your partner could become pregnant
Be at least 18 years old

To join the 2nd part of the trial, you must also have at least 1 area of cancer that doctors can clearly see and measure on a CT scan.

You cannot enter the 1st part of the trial if you have

Had radiotherapy
Finished your chemotherapy in the last few weeks - the exact amount of time that needs to have passed will depend on the drugs you had (the trial doctors can advise you about this)

You cannot enter either part of the trial if you

Have cancer that has spread to your brain or spinal cord unless this has been successfully treated, has not got any worse for at least 3 months, is not causing any symptoms and you don’t need to take steroids or medication to prevent fits (seizures)
Have had surgery in the last 4 weeks, or you are likely to have major surgery in the next 2 months
Have already had a drug similar to LDE225 – the trial doctors can advise you about this
Have had another type of biological therapy in the last 4 weeks (or earlier if you have not recovered from any side effects)
Have had another experimental drug in the last 4 weeks (or earlier if there is any chance some of the drug could still be in your body, or you have not recovered from any side effects)
Take steroids or any other drugs that damp down your immune system
Take drugs called statins or a drug to thin your blood called warfarin – it is important that you don’t stop taking any medication before talking to your doctor (they may be able to prescribe you a different drug if needed)
Need to continue to take drugs that affect body substances called cytochrome P (CYP) enzymes
Have problems with your digestive system that could affect how you absorb the trial drug
Have certain medical conditions affecting your muscles, or certain heart problems
Have an autoimmune disease or any other medical condition that could make it unsafe for you to take part
Have had any other type of cancer in the last 5 years apart from non melanoma skin cancer, carcinoma in situ of the cervix or superficial bladder cancer that have been successfully treated
Plan to start doing any type of strenuous exercise
Are pregnant or breastfeeding

Trial design

This is a phase 1 trial that will recruit about 40 people all together. The trial is in 2 parts.

In the 1st part, the researchers want to find the highest dose of LDE225 that you can safely have with gemcitabine. The first few patients taking part will have a low dose of LDE225. If they don’t have any serious side effects, the next patients will have a higher dose. And so on, until they find the best dose to give. This is called a dose escalation study.

In the 2nd part of the study, the researchers want to learn more about the side effects of LDE225 and what happens to the drug in your body. At least 12 people will join this part of the trial. They will all have the highest safe dose of LDE225 that was found in part 1.

Everybody taking part in the trial has gemcitabine and LDE225. You have gemcitabine through a drip into a vein once a week for 3 weeks out of 4. It takes about half an hour each time. You take LDE225 capsules every day. The trial team will give you a diary to keep at home. In this, you note down when you take the capsules each day.

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

The trial team will get a sample of your cancer that was removed when you had surgery or a biopsy. If there is no sample available, they will ask you to have a new biopsy Open a glossary item . They will use this, along with blood samples, to look for substances called biomarkers . These can help doctors to tell how a disease is developing or how a treatment is working. They will also use the samples to look at your DNA to learn more about genes that may cause pancreatic cancer.

During the trial, you give some extra blood samples to see how your body absorbs the drugs and how it gets rid of them. This is called pharmacokinetics Open a glossary item .

Hospital visits

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

Physical examination
Blood tests and urine tests
Heart trace (ECG )
CT scan or MRI scan

You may also have a bone scan.

You go to hospital twice in the 1st week of treatment and then once a week after that. Most visits will take no more than a couple of hours. But on 2 visits, you will be at the hospital all day to have a number of blood tests. You have a CT or MRI scan every 8 weeks.

When you finish the treatment, you go back and see the trial team within 2 weeks. As well as having a physical examination, you will have blood tests, urine tests and an ECG. You may have another scan.

A member of the trial team will contact you by phone every 2 weeks for the next 4 months to see how you are. They may ask you to have another hospital appointment at the end of the 4 months.

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

Side effects

As LDE225 is a new drug, there may be side effects we don’t know about yet. In earlier trials, the side effects have included

Taste changes and loss of appetite
Muscle spasm and aching muscles
Feeling or being sick
Tiredness (fatigue)
Hair loss

Common side effects of gemcitabine include

Flu like symptoms
Fever
Fatigue
Feeling or being sick
Poor appetite
Skin rash
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness

We have more information about gemcitabine in our cancer drugs section.