A trial looking at gemcitabine with MK-0752 to treat pancreatic cancer

The trial team found the highest, safest dose for giving MK-0752 and gemcitabine together. These will be the doses people have in future trials.

This was a phase 1 trial. It recruited 42 people who had either stage 3 or stage 4 pancreatic cancer. The aim was for everyone to have treatment with MK-0752 and gemcitabine.
 
Everyone had MK-0752 capsules once a week. To start with, they had 2 weeks of taking MK-0752 only. Then people continued to take MK-0752 once a week and also gemcitabine once a week for 3 weeks (then 1 week with no gemcitabine). So the first cycle of treatment was over 6 weeks. 

After that, each cycle was over 4 weeks with MK-0752 every week. And gemcitabine every week for the first 3 weeks of each cycle. Out of the 42 people taking part:

• 38 had combined treatment with MK-0752 and gemcitabine
• 4 people only had treatment with MK-0752 because they did not finish their first cycle and stopped treatment early 

Dose escalation
This trial tested 5 different doses of MK-0752 in combination with 2 different doses of gemcitabine. 
 
The first few patients had the lowest doses of both MK-0752 and gemcitabine. They were monitored to check they did not have any severe side effects. With each dose of MK-0752, the researchers looked at this dose alongside the 2 different doses of gemcitabine. 

The next few patients had a slightly higher dose of MK-0752 and so on, until the best dose of each drug was found. This is called dose escalation.

The trial team were able to recommend a safe dose of giving these 2 drugs together. These will be the doses people have in future trials. These were:

• MK-0752 1800mg/m2 
• gemcitabine 1000mg/m2 

Side effects
The researchers concluded that people were able to tolerate the combination of MK-0752 and gemcitabine. The side effects of having these 2 drugs together was not that different from having gemcitabine alone. The most common side effects included:

• a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness 
• loss of appetite
• feeling, or being, sick
• tummy pain (abdominal pain)
• tiredness
• liver changes
• diarrhoea

The effects of treatment on the cancer
The trial team looked at how well the treatment worked on people’s cancer. To measure this, people had scans and samples (biopsy ) taken of their cancer.

The trial team were able to measure the effect of treatment in 19 out of the 44 people who took part. All these people had cancer that had spread elsewhere in the body (stage 4 pancreatic cancer). Out of the 19 people:

• 1 person’s cancer got smaller, researchers call this a partial response
• in 13 people, their cancer stayed the same, this is called stable disease
• in 5 people, their cancer continued to grow 

The trial team also looked at how long people who had the highest safest dose of the 2 drugs lived for. They all had stage 4 cancer. They found that only 2 of the 9 people had lived for at least a year, the other 7 died sooner than this. 

Use of the FDG-PET/CT scan
The trial team also wanted to find out whether a particular scan would be useful to measure the effect of treatment. 

A PET/CT scan uses a combination of a PET and CT scan. A radioactive tracer called FDG helps to show up areas of the body where cells are more active than normal.

The first 16 patients in this trial had a FDG-PET/CT scan before and during treatment. The researchers found that this scan was not useful in measuring the response of treatment in pancreatic cancer. 

Use of CA 19-9 tumour marker
Some cancers produce substances that doctors can measure in the blood to find out if treatment is working. So if the amount is high before treatment starts and then after treatment it has come down this would show that treatment is working. Doctors call these substances tumour markers.

Some pancreatic cancers produce proteins called CA19-9. Patients in this trial had regular blood tests to measure the level of CA 19-9. 

The trial team wanted to find out whether CA 19-9 could be used to find out if treatment was working. The small numbers in this trial meant that the trial team were not able to find this out.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed ) but may not have been published in a medical journal. The figures we quote above were provided by the research team. We have not analysed the data ourselves.