A study of PDR001 alongside dabrafenib and trametinib for melanoma skin cancer
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This study is looking at a new drug called PDR001. It is for people whose melanoma:
- cannot be removed with surgery or has spread elsewhere in the body
- cells have a change in a gene called BRAF
More about this trial
Skin cells normally grow in a very orderly way. Chemical messages or signals tell them when to grow and when to stop growing. However, if a gene called BRAF becomes faulty, the protein can make skin cells grow abnormally and become cancerous. About half of all people with melanoma have a BRAF gene change (
) in their cancer cells.
The usual treatment for advanced melanoma skin cancer with this mutation is 1 of the following treatments:
- 2 drugs called dabrafenib and trametinib
- a
monoclonal antibody drug such as nivolumab or pembrolizumab
Dabrafenib and trametinib are both targeted cancer drugs called cancer growth blockers. They work in slightly different ways but both block signals that cancer cells use to divide and grow.
Nivolumab and pembrolizumab are both a type of targeted cancer drug called a monoclonal antibody. They block a protein called PD-1 and trigger the to attack and kill cancer cells.
If one of these usual treatments stops working, you might switch over to the other. But sometimes the melanoma starts to grow again. So doctors want to improve treatment.
In this study, they are looking at a drug called PDR001. It is a new treatment that blocks PD-1. Researchers want to see how well it works alongside dabrafenib and trametinib.
In this study some people have PDR001, dabrafenib and trametinib. And some people have dabrafenib, trametinib and a dummy drug (.
The main aims of the study are to:
- find out how often to give PDR001 alongside dabrafenib and trametinib
- find out how well treatment works
- learn more about the side effects
Who can enter
The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.
You might be able to join this study if all of the following apply.
- You have melanoma that has grown into surrounding tissues and nearby lymph nodes (stage 3C) and can’t be removed with surgery or it has spread elsewhere in the body (stage 4)
- You have melanoma with a BRAF V600 gene change (mutation)
- There is a sample of tissue available for the study team to test for the BRAF mutation or you are willing to have a new sample taken
- Your melanoma can be measured on your skin or a scan
- The left side of your heart that pumps blood around your body is working well
- You have satisfactory blood test results
- You can swallow tablets
- You are willing to use reliable contraception during treatment and for up to 6 months afterwards if there is any chance that you or your partner could become pregnant
- You are at least 18 years old
- You must be well enough to be up and about for at least half the day (performance status 0, 1 or 2)
You cannot join this study if any of these apply. You
Cancer related
- Have melanoma that started in the eye (uveal melanoma) or mucosal tissue (
mucosal melanoma ) - Have cancer that has spread to your brain and this hasn’t been treated or is causing symptoms. You can take part if you have no more than 3 areas of cancer that has spread to your brain, these have been treated with surgery or radiotherapy, are not getting worse and you haven’t needed to take steroids in the last 4 weeks
- Have already had treatment for melanoma that can’t be removed with surgery or spread elsewhere in the body such as dabrafenib and trametinib, chemotherapy, biological therapy, a cancer vaccine or any other treatment to your whole body (
systemic treatment ) - Have had treatment injected directly into an area of melanoma, for example talimogene laherparepvec in the last 6 months for melanoma that can’t be removed or is advanced
- Have had any cancer treatment before or after surgery for melanoma for example a targeted cancer drug such as dabrafenib and trametinib, immunotherapy such as interferon, or a tumour vaccine in the last 6 months
- Have had radiotherapy in the 4 weeks before starting study treatment or 2 weeks if it was treatment to bone lesions to help with symptoms
- Have not recovered from treatment side effects apart from hair loss unless they are mild
- Have had an experimental drug in the last 28 days or it hasn’t completely cleared your body
- Have any other cancer apart from a cancer that has been treated successfully and not come back in the last 2 years, or you have been successfully treated for non melanoma skin cancer or
carcinoma in situ
Medical conditions
- Have had problems with your
digestive system such as malabsorption syndrome or you have had major surgery to remove part of your stomach or bowel - Have a heart condition called long QT syndrome or take medication that increases the risk of developing this syndrome
- Have problems with your heart, such as a heart attack in the last 6 months, high blood pressure that is not well controlled, angina that is not well controlled, an abnormal rhythm of your heart or congestive heart failure
- Have a problem your eyes such as a blockage in a vein in your eye (retinal vein occlusion or RVO) or you are at risk of developing one for example, you have glaucoma or high pressure inside your eyes that isn’t being controlled by treatment, high blood pressure that isn’t well controlled or you have other problems with your eyes that could lead to an RVO
- Have an
autoimmune disease unless it is vitiligo, type 1 diabetes, thyroid problems that are controlled by medications or a skin condition called psoriasis that doesn’t need systemic treatment - Have had major surgery, a tissue sample taken that required a cut to get the sample (an open biopsy) or a very bad injury in the 2 weeks before starting study treatment or in the last 7 days if it was a minor operation
- Have had an organ transplant and take regular medication to damp down your immune system
- Take long term steroids or have taken medication to damp down your immune system in the 7 days before you start study treatment apart from inhalers, nose drops or eye drops
- Have a lung condition called pneumonitis or interstitial lung disease
- Have an infection that needs antibiotic treatment
- Have HIV
- Have an active hepatitis B or hepatitis C infection
- Have any other serious medical condition or mental health problem that the study team think could affect you taking part
Other
- Are sensitive or allergic to any of the study treatments or anything they contain
- Are sensitive to monoclonal antibodies and have had a bad reaction to them in the past
- Have had a live
vaccination within 4 weeks of starting study treatment - Are pregnant or breastfeeding
Trial design
This study is taking place worldwide. The researchers need about 538 people to join in total. The study is in 3 parts. Part 1 and part 2 are no longer recruiting people. Part 3 is open to recruitment.
Part 1 and 2
The aim of part 1 was to find out how often to give PDR001 in combination with dabrafenib and trametinib. The study team wanted to find out if it is better to give PDR001 every 4 weeks or every 8 weeks.
Part 2 was looking at blood and tissue samples () taken during treatment to learn more about . The study team needed between 6 and 18 people to join part 1 and 20 people to join part 2.
In part 1 and 2 everyone had dabrafenib, trametinib and PDR001. They took trametinib tablets once a day everyday. And dabrafenib capsules twice a day everyday.
They had PDR001 as a drip into their a vein. They had treatment every 4 weeks or 8 weeks, depending on when they joined part 1 or 2.
People in part 1 and 2 had treatment as long as it was helping them and the side effects weren’t too bad.
Part 3
Part 3 is the main part of the study. This part is a phase 3 study. The study team need about 500 people to join.
Part 3 is randomised. You are put into 1 of the 2 following treatment groups.
- Dabrafenib, trametinib and PDR001
- Dabrafenib, trametinib and a dummy drug (
placebo)
Neither you nor your doctor will be able to decide which group you are in. And neither of you will know if you are having PDR001 or the dummy drug. This is called a double blind study.
Dabrafenib and trametinib are tablets. You take trametinib once a day, everyday. You take dabrafenib twice a day, everyday.
You have PDR001 or the dummy drug as a drip into a vein. You have treatment every 4 weeks. This was the best treatment schedule found in part 1. The PDR001 drip takes between 30 minutes and 2 hours each time.
You continue treatment as long as it is helping you and the side effects aren’t too bad.
You have a CT scan or MRI scan:
- at week 12
- every 2 months
Samples for research
The study team will ask to take some extra blood samples. They plan to look at:
- what happens to PDR001 in the body (
pharmacokinetics ) - substances called
biomarkers to help work out why treatment might work for some people and not for others
The doctors will ask to take some extra tissue samples. But you don’t have to agree to this if you don’t want to. You can still take part in the study.
Quality of life
The study team will ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire will ask about side effects and how you’ve been feeling. This is called a .
Hospital visits
You see a doctor and have some tests before you can take part. These include:
- a physical examination
- blood tests
- an eye examination
- heart trace (
ECG ) - heart scan (
echocardiogram ) or MUGA scan - MRI scan or CT scan of your chest, tummy (abdomen) and the area between your hips (pelvis)
The study team take photographs of any unusual looking marks or lesions on your skin.
You might also have a tissue sample of your melanoma taken if you haven’t had one done in the 3 months before joining the study.
You go to hospital to have PDR001 or the dummy drug. You take your dabrafenib and trametinib tablets at home. The study team give you a fresh supply of tablets each month.
During treatment you see the doctor for check ups and some blood tests. To begin with these visits are every 2 weeks for 2 months.
After this, you have a check up once a month for all parts of the study.
When you finish treatment, you see the study team a month later. They repeat some of the tests you had done when you joined the study. They will then follow you up for 5 months to see how you are getting on. This might be at a routine hospital appointment or they might phone you at home to see how you are getting on.
Side effects
Only a very small number of people have had PDR001. So there might be some side effects we don’t know about yet. The study team will monitor you during the time you have treatment and you’ll have a phone number to call them if you are worried about anything.
The possible side effects are:
- a drop in white and red blood cells causing an increased risk of infection, tiredness and breathlessness
- high temperature (fever) and chills
- a cough
- diarrhoea or constipation
- skin rash or itchy skin
- feeling or being sick
- sore, dry mouth
- tiredness (fatigue) and feeling weak
- loss of appetite and weight loss
- swelling in the face, arms or legs
- sore joints or muscles
- nerve pain
- headaches
- feeling dizzy
- tummy (abdominal) pain
- low levels thyroid hormones causing tiredness or constipation
- high levels of thyroid hormones causing restlessness, anxiety and weight loss
- passing urine a lot or feeling thirsty due to high levels of blood sugar
- changes to blood tests that check how the liver is working
The most common side effects of having dabrafenib and trametinib together include:
- high temperatures (fever)
- a drop in the number of white blood cells causing an increased risk of infection
- skin rash, dryness or itchiness
- bleeding
- changes to blood tests that check how the liver is working
- high blood pressure
- inflamed throat or inside of the nose
- chills
- dizziness
- constipation or diarrhoea
- feeling or being sick
- sore muscles or joints
- tiredness or weakness
- loss of appetite
- cough
- swollen arms or legs
- headache
- tummy (abdominal) pain
- leg or arm pain
Your doctor will explain all the possible side effects before you join the study.
You should avoid having grapefruit, Seville oranges or any products containing the juice during the study and in the 7 days before you start treatment.
We have more information about dabrafenib.
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.
Chief Investigator
Dr. James Larkin
Supported by
Novartis
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
