A trial looking at ceritinib for people who have cancer with a change in the ALK gene (ASCEND 1)

Cancer type:

All cancer types

Lung cancer

Non small cell lung cancer

Status:

Results

Phase:

Phase 1

This trial looked at whether ceritinib can stop the growth of cancers that have a change to a gene called ALK.

More about this trial

Cells normally grow in a very orderly way. Chemical messages or signals tell them when to grow and when to stop.

In cells that have a change to a gene called the anaplastic lymphoma kinase (ALK) gene, the ALK enzyme can send signals to cancer cells telling them to grow. Several different cancers can have a change in the ALK gene including lung cancer, breast cancer and bowel cancer.

In this trial, researchers looked at a type of cancer growth blocker called ceritinib (also called Zykadia or LDK378). Ceritinib stops the ALK enzyme sending signals to cancer cells to tell them to grow. It is called an ALK inhibitor. Researchers hoped that blocking this enzyme would stop the cancer growing.

We know from laboratory research that ceritinib can stop the growth of cancer cells with the altered ALK gene. But this was the first time it had been tested in people.

The aims of the trial were to:

find the best dose of ceritinib to use
learn more about what happens to ceritinib in the body
learn more about the side effects
look at how well it works

Summary of results

This trial had two parts. Part 1 looked at the best dose of ceritinib to give. Part 2 looked at how well ceritinib works for non small cell lung cancer (NSCLC).

Part 1
The research team published results of part 1 in 2014. This part of the trial recruited 130 people. Everyone taking part had a change in the ALK gene. Most of the people taking part (94%) had advanced non small cell lung cancer.

The first few people taking part had the lowest dose of ceritinib. They didn’t have any serious side effects, so the next few people had a higher dose. And so on, until the research team found the best dose to give. This is called a phase 1 dose escalation study.

The side effects people had depended on which dose of ceritinib they had. About half the people taking part had side effects classed as serious, but they got better after treatment stopped. The most common side effects were:

diarrhoea
feeling or being sick
dehydration
a change in liver function tests

The research team also looked at how well treatment worked, and found that the cancer got smaller in about 6 out of 10 people who had the higher doses. They used this information to help decide which dose was best.

Part 2
The research team published results of part 2 in 2016. This part recruited 246 people with advanced non small cell lung cancer and a change in the ALK gene. This included some people who were in part 1 of the trial. Of these 246 people:

163 people (66%) had had a similar treatment (such as crizotinib) before
83 people (34%) had not had a similar treatment before

Everyone in this part had the same dose of ceritinib. They continued to take ceritinib tablets until their cancer started to grow or they had serious side effects.

The research team looked at how well the treatment worked. They found that the cancer went away or got smaller in:

92 out of 163 people (56%) who’d had a similar treatment before
60 out of 83 people (72%) who had not had a similar treatment before

When they looked at how many people lived at least a year after joining the trial, it was:

nearly 7 out of 10 people (67%) who’d had a similar treatment before
more than 8 out of 10 people (83%) who hadn’t had a similar treatment before

117 out of 246 people (48%) had at least one side effect that was classed as serious. The side effects were similar to those seen in part 1, and included:

diarrhoea
feeling or being sick
a change in liver function tests

The research team concluded that ceritinib was a useful treatment for people with non small cell lung cancer and a change in the ALK gene. They suggest it could be a treatment either after or instead of another similar treatment.

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.