A trial of methotrexate for cancer that has spread in people with a faulty MSH2 gene (MESH)

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

Cancer type:

Bladder cancer

Bowel (colorectal) cancer

Colon cancer

Rectal cancer

Stomach cancer

Transitional cell cancer

Womb (uterine or endometrial) cancer

Status:

Closed

Phase:

Phase 2

This trial is looking at the chemotherapy drug methotrexate for people with a change to a gene called MSH2. It is for people who have

Bowel cancer
Stomach cancer
Womb (endometrial) cancer
Bladder cancer, or cancer that stared in the lining of the urinary system (urothelium )

Every cell contains DNA. This is the genetic information which controls how cells behave. In cancer cells, the DNA is changed or damaged. Cancers can have different types of changes in the DNA. One of these is when a gene Open a glossary item called MSH2 is not working properly.

Doctors often use chemotherapy to treat cancer. But sometimes the cancer comes back after treatment and spreads elsewhere in the body.

Methotrexate is a chemotherapy drug that is used to treat some types of cancer. We know from research that methotrexate kills cancer cells when the MSH2 gene is not working properly. Researchers want to find out if it will help people with a faulty MSH2 gene who have cancer that has spread.

The aims of this trial are to

See how much methotrexate helps people in this situation
Learn more about the side effects

Who can enter

You can enter this trial if you

Have cancer that started in your bowel, stomach, womb, bladder or urothelium and has grown into surrounding tissue, or has spread elsewhere in the body
Have cancer that did not respond to, or has come back after, treatment with standard chemotherapy, or you cannot have standard treatment for some reason
Have a MSH2 gene fault (the doctors will do tests to confirm this)
Have satisfactory blood test results
Are well enough to take part in the trial (performance status 0, 1 or 2)
Are at least 18 years old
Are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance you or your partner could become pregnant

You cannot enter this trial if you

Have already had treatment with methotrexate unless it was for a non cancerous condition and you finished treatment at least 5 years before you were diagnosed with cancer
Have had any other cancer in the last 10 years apart from non melanoma skin cancer or carcinoma of the cervix and the trial doctor thinks this could affect you taking part in this trial (If you have Lynch syndrome, you may be able to take part if you have had other cancers - the doctors will advise you on this)
Have had radiotherapy to a single area of cancer (a lesion) that the researchers will be measuring in this trial, unless the lesion has got bigger since you had radiotherapy
Have another medical condition that cannot be controlled with medication
Are pregnant or breastfeeding

Trial design

This phase 2 trial will recruit 56 people. Everybody taking part will have methotrexate.

You have methotrexate as an injection into a vein. The treatment only takes a few minutes. You have another injection a week later and then 2 weeks without any treatment. Each 3 week period is called a cycle of treatment. You have up to 6 cycles of treatment. But if the treatment is helping you, your doctor may talk to you about having it for longer.

During the trial, the researchers will take samples of blood, urine and a hair follicle (such as from an eyebrow). And they will get a sample of the tissue taken when you had surgery to remove your cancer or when you had a biopsy Open a glossary item .

The researchers will use the samples to try to find substances they can measure in the body to help them tell how well the treatment is working. They call these substances biomarkers Open a glossary item . And they will use the blood samples to look at your genes . This is to learn more about how genetic changes can lead to cancer and whether certain changes affect how people respond to treatment.

The trial team may also ask your permission to take an extra biopsy during treatment. This is to learn more about what effect the treatment has on the genetic make up of your cancer. If you don’t want to have this extra biopsy, you don’t have to. You can still take part in the trial.

All samples will be stored safely and may be used in the future, but only for research purposes.

You will be asked to fill out a questionnaire before you start treatment, just before the 2nd and 4th cycle of chemotherapy, and every 3 months for a year after you finish treatment. The questionnaire will ask about any side effects you have had and how you have been feeling. This is called a quality of life study.

The trial team will also ask you to fill out a short questionnaire which asks about other members of your family who have had cancer.

People taking part in this trial may also be asked to join extra studies looking at PET scans and MRI scans. Doctors want to find out if these scans can provide more information about bowel cancer with a faulty MSH2 gene.

You may be able to take part in one or both of these studies. Whether or not you are asked to take part will depend on where you are having your treatment and also where in your body the cancer is.

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include

Physical examination
Blood tests
CT scan
Chest X-ray
Heart trace (ECG )

You go to hospital twice in each 3 week cycle of treatment. You have regular blood tests. And after 9 weeks of treatment you have a CT scan to check that your cancer has not got any bigger. If the scan shows the cancer has grown, you will stop having the trial treatment and the doctors will discuss other treatment options with you. If the cancer has stayed the same size or got smaller, you will have the next 3 cycles of treatment and then another CT scan.

After you finish treatment you will see the trial doctors and have a CT scan every 3 months for up to 1 year.

If you do take part in the MRI or PET scan study (or both), you will have extra scans

Before you start treatment
After 2 weeks of treatment
When you finish treatment

Having an MRI scan takes about 15 to 30 minutes. If you have PET scans, you have an injection of a small amount of a radioactive drug first. Then you have to wait an hour before having the scan. The scan itself can take up to an hour.

Side effects

The side effects of methotrexate include

A drop in the number of blood cells causing an increased risk of infection, tiredness, shortness of breath, bruising and bleeding problems
Loss of appetite
Sore mouth
Diarrhoea
Skin changes
Changes to how well your kidneys work
Feeling tired and weak (fatigue)
Sore eyes