A study to see if bortezomib and an epilepsy drug could be a treatment for melanoma or bowel cancer

Please note this trial is no longer recruiting patients.

This study is to find out how small doses of bortezomib (Velcade) and the epilepsy drug sodium valproate work in people with melanoma or bowel cancer. There are different treatments for both of these cancers, but doctors are always looking for ways to improve treatment.

Researchers know that sodium valproate blocks enzymes called histone deacetylases, which cells need to grow and divide. This may help to stop cancer growing. Bortezomib is a biological therapy called a proteasome inhibitor. Proteasomes help to break down proteins that the cell doesn’t need. Bortezomib blocks the proteasomes so that proteins build up in the cell. The cell then dies.

Early research into using drugs like sodium valproate for cancer has shown promising results. Research also suggests that bortezomib works well with these types of drugs to improve how well treatment works overall. This study is looking at small doses of bortezomib and sodium valproate to see how they act on bowel cancer and melanoma. It will also

See what effects these drugs have on the body when you have them separately or together
Find characteristics or ‘markers’ that help us understand why people respond to treatment differently
Find the best way to give these drugs

Please note - You will not have any direct benefit from taking part in this study, and it is unlikely to change your treatment plan in any way. But the results of the study will be used to help people with cancer in the future.

Recruitment

Start 21/08/2009

End 09/12/2011

Phase

Phase 2

Who can enter

You can enter this trial if you

Are able to have surgery for bowel cancer (colorectal cancer) OR for melanoma skin cancer that has spread to your lymph nodes or another part of your body (stage 3 or 4 melanoma) or melanoma that has spread, but your doctors don’t know where it started
Are willing to use reliable contraception if there is any chance that you or your partner could get pregnant
Are fully active (performance status 0 or 1)
Have satisfactory blood tests
Are at least 18 years old

You cannot enter this trial if you

Are pregnant or breastfeeding
Have had immunotherapy to treat your cancer in the last 4 weeks
Have had chemotherapy for advanced cancer as a tablet or through a drip into a vein (systemic treatment)
Have any other cancer, apart from successfully treated carcinoma in situ of the cervix or non melanoma skin cancer
Have hepatitis B, hepatitis C or HIV
Have had treatment in another clinical trial in the last 28 days
Have a severe lung condition called diffuse infiltrative pulmonary disease – you can check this with your doctor
Have a severe heart condition called diffuse infiltrative pericardial disease – you can check this with your doctor
Have liver problems, or are at risk of liver problems – you can check this with your doctor
Have a condition that causes red blood cells to build up in your body (porphyria)
Are allergic to sodium valproate or bortezomib
Have any other medical condition which would make you unwell if you took part, or affect the results of the study – you can check this with your doctor

Trial design

Everyone taking part in this study will be due to have surgery. This will have already been planned for you and is not part of the study.

This study will recruit 42 people into 2 groups. One group is for people with either melanoma or melanoma of unknown primary, and the other group is for people with bowel cancer.

Each group will then be split into 3 more groups. The group you are in will depend on when you join the study.

If you are one of the first 7 people for each cancer type (group 1), you will have sodium valproate tablets 3 times a day for 5 days before your surgery.

If you are one of the next 7 people for each cancer type (group 2), you will have sodium valproate 3 times a day for 5 days before your surgery. You will also have bortezomib as an injection into a vein the day before your surgery.

If you are one of the last 7 people for each cancer type (group 3), you will just have bortezomib, in the same way, the day before your surgery.

As well as taking the study medication, everyone will give some blood for the study, and a piece of their cancer tissue which will be removed during surgery. The study team will also ask if you would be willing to give them an extra sample of cancer tissue (a biopsy) when you start the study medication. You do not have to if you don’t want to. You can still take part in the study.

Hospital visits

Before you start the study, you will see the doctor and have some tests. These tests include

Height, weight, blood pressure, pulse and temperature
Blood tests
Heart trace (ECG)
Pregnancy test (if appropriate)

If you are in groups 1 or 2, you will visit the hospital 5 days before your surgery. This is to have your sodium valproate and optional biopsy.

If you are in groups 2 or 3, you will visit the hospital the day before your surgery to have bortezomib.
Everyone will also visit the hospital 2 weeks and 4 weeks after surgery to have a blood test.

Throughout this time, you will stay under the care of your regular cancer specialist in the same way as if you were not in the study.

Side effects

Common side effects of sodium valproate include

Feeling sick
Diarrhoea (taking the valproate with or after food will help this)
Temporary changes to the way your liver works
Feeling drowsy
Skin rash
Allergic reaction

Common side effects of bortezomib include

An increased risk of getting an infection
A drop in blood cells
Loss of appetite
Problems sleeping
Feeling anxious
Tingling in fingers and toes
Headache
Blurred vision
Changes in your blood pressure

Because you are having just one dose of bortezomib, the study team expect that these side effects will be milder than you if you were having the usual course. You can find out more about the side effects of bortezomib (Velcade) on CancerHelp UK.