A trial looking at treatment for children and teenagers with germ cell tumours (GC 2005 04)

Cancer type:

Children's cancers

Status:

Results

Phase:

Phase 3

This trial looked at improving the treatment for children and young adults with germ cell tumours that weren’t located in the brain.

This trial was for children and young adults up to 18 years old. We use the term ‘you’ in this summary, but of course if you are a parent, we are referring to your child.

This trial was open for people to join between 2005 and 2009. These results were published in 2019.

More about this trial

Germ cell tumours are quite rare but are more common in children and young adults. The tumours begin in cells that normally develop into the reproductive cells of the body that is the eggs and sperm. Therefore, most germ cell tumours develop in the ovaries or testicles.

But during development of the baby in the womb cells can travel to other parts of the body. And so these tumours can develop elsewhere, for example at the base of the spine near the tailbone or in the chest.

Some germ cell tumours are benign Open a glossary item (non-cancerous). And others are malignant (cancer) which can spread to other parts of the body. The benign germ cell tumours such as mature or immature teratoma are treated with surgery only in children and young adults.

The type and amount of treatment needed for malignant germ cell tumours is based on factors including:

the type of tumour
location of the tumour
age of the person
level of substances in the blood made by the tumour (tumour markers)
and if the tumour has spread and how far

If a malignant germ cell tumour can be completely removed by surgery then further treatment may not be required. If this is not the case, chemotherapy is required in addition to surgery. The treatment works well in most children and young adults as it cures 9 out of 10 cancers. But doctors want to improve on this.

Doctors know chemotherapy has side effects and because of this, they wanted to find out if having less chemotherapy, or none at all, could still cure these children while reducing long term side effects of treatment.

They wanted to do this using a chemotherapy combination that contained carboplatin instead of cisplatin known as JEB. This has already successfully used to treat children’s germ cell tumour in other studies. This combination caused less damage to hearing and kidneys.

Some germ cell tumours produce substances (markers) while the tumours are still active. You have a blood test to measure the amount of markers that the tumours are making. These markers are:

AFP (alpha feta protein)
HCG (human chorionic gonadotropin)

Doctors use these marker levels to find out if treatment is working and whether the tumour is still active. The marker levels can be used along with scans of the child and young adult to decide whether the tumour has gone (known as complete remission).

Before this trial children and young adults in the UK had chemotherapy until they achieved remission and then went on to have 2 more cycles of chemotherapy Open a glossary item .

In this trial doctors wanted to decide on the amount of chemotherapy in a different way. They looked at:

where the tumour started
type of tumour
whether it had spread or not
if it had been completely removed
age of the child or young adult
level of AFP in the blood

They used these factors to define risk groups and how much treatment each group should have. This meant some children and young adults had less chemotherapy than they would've had in the past. And this could reduce the side effects they had.

As well as the malignant germ cell tumours, the trial team also looked at children and young adults with benign teratoma. They followed them after their surgery to find out more about what happened after treatment.

Summary of results

The trial team found that children and young adults with germ cell tumours could be successfully treated using JEB (carboplatin containing) chemotherapy based on their risk group.

About this trial
This was a phase 3 trial. Of the133 children and young adults who joined the trial:

86 had a malignant germ cell tumour
47 had a teratoma

Germ cell tumour
For those who had a malignant germ cell tumour, the team worked out how likely it was for their tumour to come back or spread further after surgery.

From this the trial team put them into risk groups:

not very likely to come back (low risk)
might come back or spread further (intermediate risk)
very likely to come back or spread further (high risk)

The treatment they received was based on which risk group they were in. Those in the:

low risk had no chemotherapy after their surgery but were checked regularly
intermediate risk group had 4 courses of chemotherapy treatment
high risk group had 6 courses of chemotherapy treatment

Those having chemotherapy had a combination called JEB. This is made up of 3 drugs:

Those whose tumours made AFP had regular blood tests to check the level of AFP. The other patients had scans during the treatment. Everyone had scans at the end of their treatment.

Everyone was monitored for side effects during treatment and after treatment had been completed.

Results of the trial

Teratoma
In this trial, 47 children and young adults had a benign teratoma. The main treatment for these patients was surgery. After surgery they had regular blood tests to check the level of AFP and scans if the teratoma wasn’t completely removed by surgery.

The average follow up was just over 5 years.

3 children and young adults went on to have JEB chemotherapy. In 1 of these people, it was because their tumour had become cancerous (malignant).

Malignant germ cell tumour

The average follow up for all 86 children and young adults in the study was just over 6 years.

After their surgery:

25 patients had no chemotherapy (low risk group)
23 patients had 4 courses of chemotherapy (intermediate risk group)
38 patients had 6 courses of chemotherapy (high risk group)

The cancer came back in 7 patients in the low risk group. They then had chemotherapy which worked well and there was no sign of their cancer.

5 years after treatment the trial team wanted to know how many children and young adults were alive.

All of the 25 children and young adults (100%) in the low risk group were alive.

22 of the 23 children and young adults (96.4%) in the intermediate group were alive.

36 of the 38 children and young adults (94.7%) in the high risk group were alive.

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They also looked at the number of children and young adults in each group who were alive at 5 years with no sign of the tumour coming back in this time.

For those in the low risk group it was 18 of the 25 children and young adults (72%).

For those in the intermediate group it was 21 of the 23 children and young adults (92.9%).

For those in the high risk group it was 35 of the 38 children and young adults (92.1%).

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AFP blood results and treatment
Of the 133 children and young adults in the trial, 2 had their treatment changed due to their AFP blood results.

For 1 child with a germ cell tumour the AFP was dropping slowly. And so they had more JEB chemotherapy.

During follow up 1 child with a teratoma had a raised AFP blood test result. Their tumour had changed from being non cancerous (benign) to cancerous (malignant). And they had JEB chemotherapy for this.

Side effects
The team looked at the most common and worst side effects of JEB chemotherapy. These were:

drop in blood cells causing an increased risk of infection, bruising and bleeding
high temperature and low numbers of white blood cells
being sick
low levels of potassium in the blood
low levels of phosphate in the blood
low levels of magnesium in the blood
changes to how well the liver worked
serious bleeding
loss of appetite
diarrhoea
changes to how well the lungs worked
changes to how well the kidneys worked
hearing loss

The results showed that side effects during treatment could be treated successfully. And there were no side effects after treatment during follow up.

Conclusion

The trial team concluded that the treatment approach they used for malignant germ cell tumours in children and young adults was successful for nearly all the patients in the study by:

using chemotherapy treatment containing carboplatin
using risk grouping based on how likely it was for the germ cell tumour to come back or spread

This approach seems to reduce long term effects from treatment.

A new international trial called COG AGCT 1531 is in the process of being opened in the UK. This will compare chemotherapy treatment using carboplatin with the standard chemotherapy treatment Open a glossary item using cisplatin.

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.