A trial of pembrolizumab and a new drug called guadecitabine for people with solid tumours (HyPeR)

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

Cancer type:

All cancer types

Secondary cancers

Status:

Closed

Phase:

Phase 1

This trial is for people with a solid tumour that has spread or continued to grow despite treatment (refractory). A solid tumour is any type of cancer apart from those of the blood or lymphatic system such as:

leukaemia
lymphoma
myeloma

More about this trial

Researchers are looking for new ways to help people with solid tumours that have spread or continued to grow despite treatments. In this trial they are looking at a new drug called guadecitabine.

Guadecitabine is a type of drug called a demethylating agent. It helps the immune system to spot the cancer, which helps pembrolizumab to work better.

Guadecitabine is similar to a drug called decitabine. Decitabine is already a possible treatment for people with acute myeloid leukaemia (AML). Doctors think that guadecitabine might work better than decitabine, but they need to find out for sure.

Pembrolizumab (Keytruda) is a targeted drug called a monoclonal antibody. It stimulates the immune system to fight cancer cells. Pembrolizumab is already a possible treatment for people with non small cell lung cancer (NSCLC) and melanoma.

This trial is in 2 parts. In the first part, researchers wanted to find the best dose of guadecitabine that you can safely have with pembrolizumab. This part is now closed. Researchers are now looking for people to join part 2.

In the second part of this trial, everyone has the best dose of guadecitabine and pembrolizumab found during part 1. Doctors want to find out how well pembrolizumab and guadecitabine work and the effect it has on the body.

Who can enter

The following bullet points list 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 this trial if all of the following apply:

you have a solid tumour (not a leukaemia, lymphoma or myeloma)
you have had standard treatment but they stopped working and your doctor thinks there isn’t a suitable treatment for you or you don’t want to have more standard treatment
you are well enough to carry out all your normal activities, apart from heavy physical work (performance status 0 or 1) and this hasn’t changed in the past 2 weeks
you are willing to have tissue samples of your cancer taken before the start of treatment and during treatment
you have at least 1 area of cancer that can be measured on a scan
you have satisfactory blood test results
your heart is working well
you are at least 18 years old
you are willing to use reliable contraception during treatment and for 6 months afterwards if there is any possibility that you or your partner could become pregnant

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

have had radiotherapy unless it was to help with symptoms (palliative radiotherapy) in the past 4 weeks
have had hormone treatment, chemotherapy, immunotherapy or treatment that was part of a clinical trial in the past 4 weeks (6 weeks if you had treatment with nitrosoureas or mitomycin C)
have another cancer that is getting worse or that needs treatment, apart from successfully treated non melanoma skin cancer or carcinoma in situ of the bladder and cervix
have cancer spread in your brain or the spinal cord unless you have had treatment, it hasn’t got worse in the past 4 weeks and you are no longer taking steroids
still have moderate or severe side effects from previous cancer treatment apart from hair loss

Medical conditions

You:

have taken drugs that damp down your immune system such steroids in the past 2 weeks, unless it was a very small amount
have or have had an autoimmune disease that needed treatment that reached your whole body (systemic) in the past 3 months, apart from treatment to replace something the body makes
have had moderate or severe side effects to previous immunotherapy treatment
have had lung problems such as interstitial lung disease or inflammation of the lung (pneumonitis)
have heart problems such as high blood pressure that isn’t controlled or you have had a heart attack in the last 6 months
have an infection that needs systemic treatment
have had a live vaccine in the past month
have had a major surgery and you still have side effects from it
have HIV
have hepatitis B or hepatitis C
have any other serious medical condition that the trial team think could affect you taking part

Other

You:

are pregnant or breastfeeding
are known to be sensitive to any of the drugs used in this trial or anything they contain
are taking part or are going to take part in another clinical trial

Trial design

This is a phase 1 trial. Researchers need up to 35 people to take part.

This trial has 2 parts:

part 1 is called dose escalation - this part is now closed
part 2 is called dose expansion

Everyone has guadecitabine and pembrolizumab. The dose of guadecitabine you have depends on when you join the trial.

Part 1

The first few people taking part have a low dose of guadecitabine and the normal dose of pembrolizumab. If they don’t have any serious side effects, the next few people have a higher dose of guadecitabine and the normal dose of pembrolizumab. And so on until doctors find the best dose of guadecitabine.

Doctors need between 6 to 12 people to join this part of the trial.

You have treatment in cycles. Each 3 week period is called a cycle of treatment. The 1st day of each cycle of treatment is the day 1.

You have the first cycle of treatment in the following way:

you have guadecitabine as an injection under your skin (subcutaneous) every day, from day 1 until day 4
you have no treatment from day 5 until day 21

You then start the next cycle of treatment. You have the 2nd cycle of treatment in the following way:

you have guadecitabine as an injection under your skin every day, from day 1 until day 4
you have no treatment from day 5 until day 7
you have pembrolizumab as a drip into your vein for 30 minutes on day 8
you have no treatment from day 9 until day 21

After the 2nd cycle, you have the rest of your treatment in the following way. You have:

pembrolizumab as a drip into your vein on day 1
guadecitabine as an injection under your skin every day, from day 1 to day 4
no treatment from day 5 to day 21

You continue to have treatment for as long as it is helping you and the side effects aren’t too bad. You can have treatment for up to 2 years.

Part 2

Everyone taking part has the best dose of guadecitabine found in part 1, and the normal dose of pembrolizumab. Doctors need around 20 people to join this part of the trial.

You have treatment for each cycle in part 2 as follows:

pembrolizumab as a drip into your vein on day 1
guadecitabine as an injection under your skin every day, from day 1 to day 4
no treatment from day 5 to day 21

You continue to have treatment for as long as it is helping you and the side effects aren’t too bad. You can have treatment for up to 2 years.

Blood tests

You have extra blood tests as part of this trial. You have them before the start of treatment, at set times during the trial and at the end of treatment.

Doctors want to:

look for certain proteins (biomarkers) that can tell how well the treatment works
measure the levels of guadecitabine in your body

Tissue sample

The trial team will ask to use a tissue sample taken at the time of your diagnosis or during cancer treatment.

You also need to have extra tissue samples taken (biopsies). You have one biopsy before you start the trial, one during the trial and one when you complete your trial treatment.

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

physical examination
heart trace (ECG)
blood tests
urine tests
a CT scan or MRI scan

During treatment, you see the trial doctor every week for the first 3 weeks. You then see them every 3 weeks. You have a physical examination and blood tests every time you see them.

You have a CT scan or MRI scan every 9 weeks. This continues for as long as your cancer stays the same and the side effects aren’t too bad. If your cancer gets worse you stop having guadecitabine and pembrolizumab.

When you finish treatment, you see the trial team after a month. You continue to see them every month until all the side effects disappear.

You then see your medical team as part of your standard care.

Side effects

Guadecitabine is a new drug, so there might be side effects we don’t know about yet.

The trial team monitor you during the time you have treatment. You have a phone number to call if you are worried about anything. The team will tell you about all the possible side effects before you start the trial.

The possible side effects of guadecitabine include:

a drop in the number of blood cells that increases your risk of infection, breathlessness, bruising and bleeding
diarrhoea or constipation
feeling or being sick
dry mouth and taste changes
skin problems such as skin rashes, dry skin and itching
hair loss
tiredness (fatigue)
tummy (abdominal) pain and indigestion
loss of appetite and weight loss
infections such as pneumonia
lung problems such as cough
dizziness and headaches
fever and chills
muscle, bone and joint pain
fluid build up (oedema)