A trial looking at two different types of intensive treatment for neuroblastoma that has spread (VERITAS)

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

Cancer type:

Children's cancers

Neuroblastoma

Status:

Closed

Phase:

Phase 2

This trial is comparing high dose chemotherapy with molecular radiotherapy and chemotherapy. It is for children and young people with neuroblastoma that has spread.

Cancer Research UK supports this trial.

More about this trial

This trial is for children and young people with neuroblastoma that has:

spread somewhere else in the body
not responded well to their first course of treatment

We use the term 'you' in this summary, but if you are a parent, we are referring to your child.

The first treatment (induction treatment) for neuroblastoma that has spread is chemotherapy. This is to either get rid of, or reduce, the cancer spread. But this does not work so well in a small number of children and young people. Their neuroblastoma does not respond well enough to this chemotherapy. We know from research that this means their neuroblastoma is more difficult to treat.

There is no standard treatment Open a glossary item for children and young people in this situation. Possible treatments include one or more of the following:

different types of chemotherapy
high dose chemotherapy with your own stem cells back (autologous stem cell transplant)
radiotherapy
surgery

Doctors would like to know which treatment, or treatment combinations, are best.

The researchers are comparing two different types of intensive treatment. These are:

high dose thiotepa – a type of chemotherapy
131-I-mIBG (a type of molecular radiotherapy) with topotecan (a type of chemotherapy)

Molecular radiotherapy is when a substance called metaiodobenzylguanidine (mIBG) is added to radioactive iodine (131-I). It’s used to deliver targeted radiation therapy. The mIBG is picked up by the cancer cells. The dose of radioactive iodine attached to the mIBG is high enough to kill the neuroblastoma cells. But generally, the treatment does not cause serious side effects to surrounding tissues.

The aims of this trial are to find out:

if high dose thiotepa, or molecular radiotherapy with topotecan, works better for intensive treatment
how safe the treatment is
more about side effects of the treatment

Who can enter

The following bullet points are a summary of 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 neuroblastoma that has spread to another part of the body
have had treatment for high risk neuroblastoma, either on a study called the High Risk Neuroblastoma SIOPEN study, or standard treatment for very high risk neuroblastoma. Your doctor can explain more about risk groups.
have neuroblastoma that has not responded as well as hoped following induction chemotherapy
have cancer that your doctors could see on an mIBG scan when you were diagnosed
have cancer that your doctors could see on an mIBG scan after your first chemotherapy schedule (induction chemotherapy)
can care for yourself but can’t carry on with all your normal activities or do active work (Karnofsky performance status more than 70), or for young children they can't play as energetically as normal and spend less time than usual in play activity (Lansky scale is more than 70)
have satisfactory blood test results
are willing to use reliable contraception while taking the study treatment and for one year after the study drug, if you or your partner could become pregnant
were between 1 and 21 years old when you were diagnosed with neuroblastoma

Who can’t take part

You cannot join this trial if any of these apply. You:

have neuroblastoma which is continuing to grow too much despite initial treatment, your doctor can explain more about this
have cancer that has spread to tissue in the brain called parenchyma
have had high dose chemotherapy and your own stem cells back before
have had any cancer treatments other than certain common treatments for high risk neuroblastoma – you trial doctor can explain more about these treatments
have shortness of breath
have lower levels of oxygen in your bloodstream (less than 95% in air measured by pulse oximetry)
have problems with your heart function, including your heart not pumping blood as well as it should. You will have heart function tests before you take part
have long term inflammatory bowel disease or you have a bowel obstruction
have a serious illness or infection which the trial team think could prevent you from taking part
have recently had the yellow fever vaccine or a live vaccine
are allergic to any of the study drugs or anything they contain
are allergic to dacarbazine
are allergic to peanut or soya
are taking St John’s Wart
are pregnant or are breastfeeding

Trial design

This is a phase 2 trial. The researchers hope 150 children and young people will take part in the UK and Europe. It has 4 stages. Apart from stage 3, everyone taking part has the same treatment.

Stage 1 - Chemotherapy stage (initial chemotherapy)

Everyone has irinotecan and temozolomide. You have treatment in cycles and each 21 day period is a cycle of treatment. You:

have irinotecan through a drip into the bloodstream over one hour
take temozolomide capsules on an empty stomach

You have treatment every day for the first 5 days of each cycle. And you have 3 cycles in total.

You have chemotherapy into the bloodstream through a long flexible plastic tube called a central line. This can stay in while you are taking part in the trial and is used for:

treatment
taking blood samples

Stage 2 - Collecting your stem cells

Everyone taking part has their stem cells collected from your bloodstream through a drip. This usually takes a few hours. Collecting your stem cells means doctors can then use your own stem cells to replace blood cells destroyed by high doses of chemotherapy and other treatments.

After the chemotherapy stage, you have injections of a growth factor every day. Growth factors are natural substances that make the bone marrow produce more stem and blood cells.

Once you have enough stem cells, these are collected from your bloodstream through a drip. They are then frozen and stored.

Stage 3 – First intensive consolidation treatment and stem cells back
This part of the trial is randomised. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups. For both treatments you might need to travel to a different hospital depending on where you live. Your team will discuss this with you.

The two treatment groups are:

Group A – you have 131-I-mIBG and topotecan
Group B – you have high dose thiotepa

Group A
You have both molecular radiotherapy with 131-I-mIBG and topotecan for one cycle over 19 days. You have both of these through a drip into your bloodstream. You have:

131-I-mIBG on day 1 and on day 15
topotecan over 1 hour on days 1 to 5 and days 15 to 19

Group B
You have the chemotherapy drug thiotepa at a high dose for one cycle. You have it once a day for 3 days.

Both groups
You then have some of your defrosted stem cells back. You have these through a drip into your bloodstream.

Stage 4 – Second intensive consolidation chemotherapy and stem cells back

You have this at the same hospital where you had your first intensive consolidation treatment.

Everyone has one cycle of chemotherapy with the drugs busulfan and melphalan.

This cycle takes 8 days. You have busulfan and melphalan via a drip into your bloodstream. You have this on days 1 to 5, and day 7.

You have more of your defrosted stem cells through a drip into your bloodstream.

VERITAS trial diagram

You might then have other treatments for your neuroblastoma. This might include surgery and radiotherapy. Your doctor will let you know if these are suitable treatments for you.

Hospital visits

You see a doctor and have some tests before you can take part. These include:

a physical examination
blood tests
urine tests, including a pregnancy test (if suitable)
a hearing test
lung function tests
an ECHO scan of your heart
bone marrow tests
scans such as CT scan, MRI scan, or mIBG test – which scans you have depend on where the neuroblastoma is in your body

You might need to travel to a specialist hospital for certain parts of this trial, such as for molecular radiotherapy or stem cell collection and return.

The trial team can let you know how long each treatment stage lasts. And how long you will be in hospital at different points during the trial. You will stay in hospital for about 3 or 4 weeks during your intensive treatment (stage 3).

Tests and scans during treatment

While having chemotherapy, you have the same routine tests that you would have if not taking part in the trial. These include scans and blood tests. This is to check you are well enough to have chemotherapy and how well the treatments are working.

You have extra tests at certain points during the trial. These include:

blood tests
lung function tests
an ECHO scan
a hearing test
scans such as a CT scan, MRI scan, bone scan, mIBG scan or ultrasound scan - which scans you need depend on where the neuroblastoma is in your body
bone marrow tests
a pregnancy test (if suitable)

Follow up
After treatment has finished, the trial team will monitor you for at least 3 years.

You will only need to attend routine clinic appointments for them to check how you are getting on. These are usually every 3 months for the first 3 years.

Side effects

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

Chemotherapy
Some common side effects of chemotherapy include:

increased risk of infections from low white blood cells
bruising or bleeding from low platelets
breathlessness or looking pale from low red blood cells
hair loss
feeling or being sick
diarrhoea or constipation
fever
confusion, dizziness and headache
muscle weakness or pain
joint pain
tiredness (fatigue)
loss of appetite
itchy skin
changes to the liver or kidneys
changes to your blood pressure
allergic reactions

We have information about:

131-I- mIBG treatment

Children and young people having 131-I- mIBG treatment need to be cared for on their own because of the radioactive iodine. It’s normal to feel a bit nervous about this at first. The specialist team let you know what to expect and how best you and your family might cope. Non pregnant family members can consent to staying with a younger child. The team minimise risk of radiation to other people.

The trial team will explain more about the side effects of this type of intensive treatment. Possible side effects include:

a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
a decrease in the amount of hormones the thyroid makes (hypothyroidism ) – you have regular blood tests to check for this

Stem cell collection and transplant

Your team will explain more about the possible side effects of having your stem cells collected and returned.

Generally, the main side effects of intensive treatment with a stem cell transplant include:

an increased risk of getting an infection
an increased risk of bruising or bleeding from low blood cell counts
sickness and diarrhoea
a sore mouth
difficulty eating and drinking
feeling tired and run down

There are longer term side effects of having intensive chemotherapy. Your team will talk these through with you. You have time to ask any questions you might have.