A trial looking at the drugs defactinib with VS-6766 for all cancers (FRAME) (2024)

This trial is looking at defactinib with VS-6766 for solid cancers. A solid cancer is any cancer apart from leukaemia, lymphoma and myeloma.

It is open to people who can’t have or don’t want to have the standard treatment for their cancer.

Defactinib and VS-6766 are both targeted cancer drugs . They are cancer growth blockers. They work by blocking messages that tell cancer cells to grow.

We know from research that defactinib by itself and VS-6766 by itself work against cancer.

Researchers think that the combination of these 2 drugs could work better for people with a solid cancer. To find this out they need to do a clinical trial . But before doing a clinical trial they need to find the best dose to give.

They already know what the best dose is to give of each drug by itself. They then needed to find out what the best dose is when you have them together.

There are 2 parts to this trial.

In the first part a few people have a small dose of both to start. And the next few have a larger dose until the team find the best dose to give. This is a dose escalation study . This part of the study is now complete.

After finding the best dose the team do a dose expansion study. This is the second part of the study. This part is open to people who have one of the following cancers:

• non small cell lung cancer (NSCLC)
• bowel cancer – this group is now closed
• ovarian cancer
• wombcancer (endometrial cancer) with a certain gene change
• pancreatic cancer with a certain gene change

The aims of this trial are to find out:

• the best dose of defactinib with VS-6766 to give
• the side effects and how to manage them
• what happens to these drugs in the body
• what this combination of drugs does to the body
• if this combination shrinks the cancers listed above

The following bullet points are a summary of the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join the dose escalation part of the trial if you have a solid cancer.

You may be able to join the dose expansion part of the trial if you have one of the following cancers:

• advanced non small cell lung cancer (NSCLC) with certain gene changes (mutations )
• low grade serous type ovarian cancer
• advanced endometrial cancer with certain gene changes
• advanced pancreatic cancer or pancreatic cancer that has spread to another part of the body

Your doctor can tell you more about what the gene changes are and whether you have one.

And all of the following apply. You:

• have satisfactory blood test results
• are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
• have an area of cancer that the doctor can see and measure on a scan
• have a sample of tissue (biopsy ) from when you were diagnosed and you agree to the team asking for a piece of the sample
• have a heart trace (ECG ) that shows your heart works well enough. You have a test for this and your doctor can tell you about the results.
• are willing to use contraception during the trial and for a time after if there is any chance you or your partner could become pregnant
• are at least 18 years old

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

• have cancer spread into the brain or spinal cord unless it has been treated and is not getting worse. You must also have another area of cancer that the doctor can measure that is not in the brain or spinal cord.
• have ongoing side effects from previous treatment. This is apart from hair loss or some mild side effects. Your doctor will know which side effects these are.
• are taking part or planning to take part in another clinical trial using an experimental drug
• have had treatment in the past 4 weeks (6 weeks of nitrosoureas and mitomycin C ). This is apart from radiotherapy for pain or symptom control.

Medical conditions

You cannot join this trial if any of these apply. You:

• have major surgery within 4 weeks of agreeing to take part, for minor surgery it is 2 weeks
• are taking warfarin. Unless it is for a blood clot and you can change to having heparin.
• have a liver problem called Gilbert’s syndrome
• have inflammation of the pancreas
• have hepatitis B, hepatitis C or HIV
• have certain eye problems or diseases. Your doctor will know which ones.
• have difficulty swallowing or you have a problem with your digestive system . This is a problem that affects how well your body absorbs medication taken by mouth.
• have had a heart attack in the past 6 months or you have another heart problem that could affect you taking part. Your doctor can tell you more.
• have had medication that affects the CYP enzymes within 7 days of starting treatment
• have symptoms of or have COVID-19. You might be able to join when you have fully recovered and have a test showing no signs of COVID-19. You doctor can tell you about this.
• have any other medical condition or mental health problem that your doctor or a member of the trial team thinks could affect you taking part

Other

You are pregnant or breastfeeding.

This is a phase 1 trial. There are 2 parts to this trial. The dose escalation part and the dose expansion part.

In total the team need 110 people to take part.

Dose escalation
This stage of the trial is now closed. 24 people took part in this stage.

Dose expansion
In this stage the team need 86 people. This part will look at how well the combination of defactinib and VS-6766 work for certain cancers. These are:

• advanced non small cell lung cancer (NSCLC) with certain gene changes (mutations)
• advanced bowel cancer with a certain gene change – the team have enough people in this group so it is closed to recruitment
• low grade serous type ovarian cancer
• advanced endometrial cancer with certain gene changes
• advanced pancreatic cancer or pancreatic cancer that has spread to another part of the body
• advanced solid cancer with a certain gene change – the team have enough people in this group so it is closed to recruitment

Defactinib is a tablet. You take it twice a day after a meal, that is on a full stomach.

VS-6766 are capsules. You take them twice a week. You take them either on Monday and Thursday or Tuesday and Friday. Your doctor will tell you on which days to take the capsules. You take VS-6766 on an empty stomach. So you can’t eat for at least 2 hours before taking the capsules or for an hour after you take the capsules.

You have treatment for 3 weeks and then have 1week of no treatment. This 4 week period is a cycle of treatment .

You continue having treatment as long as it is helping and the side effects aren’t too bad.

You have a diary to take home and fill in. You write down when you take your treatment and how many tablets and capsules you take. You must bring this with you to every hospital visit.

Research samples
The team ask for blood samples and tissue samples during treatment. For some groups of people in the trial you must agree to have these. For others you don’t have to agree to have them. Your doctor or a member of the trial team will tell you if you must agree to them or not.

Researchers will use these samples to find out:

• what happens to defactinib and VS-6766 in the body
• what affect they have on the body
• how well treatment is working

You see the doctor to have some tests. These include:

• a physical examination
• blood tests
• CT scan or an MRI scan
• heart trace (ECG )
• eye examination
• mouth swab

You see the doctor each week for 8 weeks (2 cycles) to see how you are and for blood tests. You then see the doctor every 4 weeks while you are having treatment.

You have a CT scan or an MRI scan every 8 weeks.

You see the doctor within a month after finishing treatment for tests. These are:

• a physical examination
• blood tests
• CT scan or an MRI scan
• heart trace
• eye examination

If you have side effects from treatment the team will follow up every month to see how you are until the side effects are gone.

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

Defactinib and VS-6766 are new drugs and there may be side effects we don’t know about yet.

The most common side effects of defactinib include:

• feeling or being sick
• tiredness and lack of energy (fatigue)
• diarrhoea or constipation
• an increase of bilirubin in the blood that can cause yellowing of the skin or whites of the eyes, dark urine
• shortness of breath
• loss of appetite
• cough
• swelling of the feet and ankles
• joint pain
• headaches

The most common side effects of VS-6766 include:

• skin rash and other skin problems
• an increased level of an enzyme in the blood that might indicate inflammation of the muscles or other serious problems
• problems with the eyes or eyesight including sore eyes and blurred vision
• inflammation of the mouth and mouth ulcers
• diarrhoea
• tiredness and lack of energy (fatigue)
• swelling of the legs
• a decrease of a protein called albumin in the blood
• feeling or being sick

There is a small chance you might have an allergic reaction to defactinib, VS-6766 or both. Contact your doctor or the health advice line if you have:

• a high temperature
• feel unwell

Or you feel any way different from the usual.

Your doctor or a member of the trial team will talk to you about the possible side effects of treatment before you agree to take part.