A trial of telotristat etiprate for people who have symptoms of carcinoid syndrome that are not controlled with other drugs (TELESTAR)

Cancer type:

Carcinoid

Neuroendocrine tumour (NET)

Status:

Results

Phase:

Phase 3

This trial looked at a drug called telotristat etiprate for people who had symptoms of carcinoid syndrome that were not controlled with other drugs.

This trial was open between 2013 and 2015 for people to join. The results were published in 2018.

More about this trial

Neuroendocrine tumours (NETs) are a rare group of cancers. Some make and release hormones and they are called functioning NETs. They are normally found in the digestive system. The most common type that causes carcinoid syndrome usually start in the bowels.

Some NETs produce serotonin which causes symptoms such as:

diarrhoea
frequent bowel movements
tummy (abdominal) pain
redness of the face (flushing)

This is carcinoid syndrome.

Doctors can treat carcinoid syndrome with drugs called somatostatin analogues. These drugs help. But they may stop working after a while. No other treatments were available if:

somatostatin analogues stopped working
people couldn't or didn’t want to take them

Researchers are looking for new treatments to help people in these situations. In this trial, they looked at a drug called telotristat etiprate. This reduces the production of serotonin.

The aims of this trial were to:

see if different doses of telotristat etiprate helped relieve symptoms of carcinoid syndrome when other drugs no longer controlled them
learn more about the side effects

Summary of results

The trial team found that telotristat etiprate helped relieve symptoms of carcinoid syndrome.

About this trial
This was a phase 3 trial. 135 people took part.

Everyone who took part was put into 1 of 3 groups. Neither they nor their doctor chose or knew which group they were in. It was a double blind randomised trial.

45 people had a low dose of telotristat etiprate
45 people had a high dose of telotristat etiprate
45 people had a dummy drug (placebo)

Everyone had 12 weeks of treatment. This was the double blind part of the trial. After this the team told everyone which group they were in.

They then had the choice to continue with telotrisat epitrate at the high dose for another 36 weeks. This is called the open label extension period.

Results

Double blind randomised part
At 12 weeks the researchers looked at the number of bowel movements people had. They looked at whether people had a durable response to treatment or a non durable response to treatment.

A durable response was if the number of bowel movements had reduced by a third for 6 weeks or more during the 12 weeks of treatment.

48 of the 135 people had a durable response:

20 people had the low dose of telotrisat epitrate
19 people had the high dose of telortrisat epitrate
9 people had the dummy drug

People who had a non durable response were those whose bowel movements hadn't reduced by a third for at least 6 weeks during the treatment time.

87 of the 135 people had a non durable response:

25 people had the low dose of telotrisat epitrate
26 people had the high dose of telotrisat epitrate
36 people had the dummy drug

Open label extension period
In this part people chose to continue with high dose telotristat etiprate for another 36 weeks.

This part included 35 people who had a durable response in the double blind randomised part. Of these 29 continued to have a durable response throughout this part.

9 people who had the dummy drug and had a durable response in the double blind randomised part continued to do so.

42 people who had telotrisat epitrate and a non durable response in the double blind randomised part continued into this part. Of these 12 people had a durable response.

29 people who had the dummy drug and a non durable response in the double blind randomised part continued into this part. Of these 16 had a durable response when they started taking telotrisat epitrate.

Quality of life
At 12 weeks people who had a durable response in the double blind randomised part also showed improvement in other carcinoid symptoms such as:

feeling or being sick
tummy (abdominal) pain
flushing
needing to go to the toilet urgently

This improvement in their symptoms continued during the open label extension part.

In both parts the symptoms of people who had a durable response improved significantly better than those who had a non durable response.

Weight changes
Weight loss might cause a decrease in the survival of people with uncontrolled carcinoid syndrome.

At 12 weeks the team looked at the number of people whose weight had changed by 3% or more. Of the 135 people they had the results for 120 people.

The team found the number of people who had gained weight was:

7 who had the low dose of telotrisat epitrate
13 who had the high dose of telotrisat epitrate
2 who had the dummy drug

The number of people who had lost weight was:

4 who had the low dose of telotrisat epitrate
6 who had the high dose of telotrisat epitrate
5 who had the dummy drug

About 32 out of every 100 people (32.5%) had a significant weight gain while taking telotrisat epitrate. This improvement could be another reason why telotrisat epitrate might work well for people with carcinoid syndrome.

Hormonal Levels
To monitor carcinoid syndrome doctors look at the level of a hormone called 5-HIAA in the blood. The trial team looked at the level of 5-HIAA in each group. They found that it had decreased by nearly a third (30%) in:

25 people (78%) in the low dose group
26 people (87%) in the high dose group
3 people (10%) in the dummy drug group

Conclusion
They say these results show a continued decrease in the number of bowel movements lead to an improvement in other carcinoid symptoms. And this leads to an improvement in their quality of life and wellbeing.

They recommend that telotristat epitrate should be considered for people with carcinoid syndrome who have severe diarrhoea. This is people who have all the following.

You have 4 or more bowel movements a day.
Your poo is either soft blobs, mushy or liquid (Bristol stool chart types 5, 6 and 7).
You have difficulty controlling when your need to go to the toilet (urgency) and or you have accidents.

Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.