A trial looking at adding AMG 102 and AMG 479 to chemotherapy for advanced small cell lung cancer

Who can enter

You can enter this trial if you

• Have small cell lung cancer
• Have cancer that has spread outside your lung (you have ‘extensive disease’)
• Have satisfactory blood tests
• Are able to have medication through a drip into a vein
• Are well enough to be up and about for at least half the day (performance status 0 or 1)
• Are willing to use reliable contraception during the trial and up to 6 months after if there is any chance that you or your partner could become pregnant
• Are at least 18 years old

You cannot enter this trial if you

• Have had any treatment for small cell lung cancer, including trial medication (if you had radiotherapy to control symptoms of cancer spread, or that didn’t cause changes to your blood cell production you may still be able to take part)
• Have cancer that has spread to your brain or spinal cord (your ‘central nervous system’ or ‘CNS’) - if you have had treatment that has brought this under control, you are well and are not waiting to have more treatment to this area you may still be able to take part
• Have had any other cancer except carcinoma in situ of the cervix or non melanoma skin cancer that have been successfully treated and you have been clear for at least 3 years, or a type of freckle called lentigo maligna or prostate cells that are abnormal but not cancerous (‘prostate intraepithelial neoplasia’)
• Have had major surgery in the last 28 days, or minor surgery in the last 7 days, or you have not recovered from surgery before this
• Have had problems with your circulation causing problems such as blood clots in your leg or lung, a stroke, a mini stroke or heart attack
• Are taking medication to treat a blood clot
• Have had problems with bleeding
• Have a serious wound or ulcer that is not healing
• Have had an infection needing treatment in the last 2 weeks (if you have had a urine, nose, throat or sinus infection you can still take part)
• Have hepatitis B or C, or HIV
• Are sensitive to any of the drugs in this trial
• Are pregnant or breastfeeding
• Have any other condition which would affect you or the results of the trial if you took part

Trial design

This is a phase 2 trial. Everyone will have etoposide chemotherapy. You will also have either carboplatin or cisplatin, depending on which your doctor thinks is best for you. About 5 people from the UK will take part in phase 2.

This part of the trial is randomised. The people taking part are put into one of 3 groups by a computer. Neither you nor your doctor will be able to decide which group you are in. You will not know which group you are in either

• If you are in group 1, you will have AMG 479 and chemotherapy
• If you are in group 2, you have AMG 102 and chemotherapy
• If you are in group 3, you have a dummy drug (placebo) and chemotherapy

All groups have treatment for the first 3 days of every 3 week cycle of treatment. You have all 3 of the drugs you are having through a drip into a vein on the first day of each cycle. Then you have etoposide alone on days 2 and 3.

If tests show that the treatment is working after 4 cycles, you will have another 2 cycles of treatment.

Then, if your cancer is responding well to the chemotherapy with trial treatment, and if you have not already had it, you will have radiotherapy to your brain. This is to kill any cancer cells that may have spread there, and is called prophylactic cranial irradiation (PCI). You stop the trial treatment for a short while to have this, then restart treatment once you have finished the radiotherapy.

After you have finished chemotherapy, and PCI if you needed it, you will continue to have the trial drug or placebo drip every 3 weeks for up to 2 years as part of the trial.

You will have regular blood tests throughout the trial. These include taking samples to look at, for example, how the trial drug is processed by the body. The team will also study the blood samples, and any pieces of tissue samples (biopsies) your doctor may have taken, to look at genes and to look for biomarkers. This may help them understand more about the cancer and how people respond to the treatment. Some of these tests are extra, so you do not have to agree to them if you don’t want to. The study team will explain more about these tests.

After you finish the trial, you will see your regular cancer specialist in the same way as you did before the trial.

Hospital visits

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

• Height and weight
• Heart trace (ECG)
• CT scan or MRI scan of your brain, chest, tummy (abdomen) and anywhere your cancer may have spread to
• Blood test
• Pregnancy test (if appropriate)

You will also fill out a questionnaire before you start treatment and regularly while you are taking the trial drug. The questionnaire will ask you about any side effects you have had and about how you have been feeling. This is called a quality of life study.

You come to hospital for 3 days in a row at the beginning of each cycle of treatment, for up to 6 cycles. You will see the doctor before you start each cycle of treatment. These visits will take 4 to 6 hours when you have more than one drug, and about 2 to 3 hours when you have one drug.

You then come to hospital every 3 weeks for up to 2 years to have the trial drug on its own. You may also need to come to hospital for some blood tests a few days before your treatment, or at other times – the trial team will tell you if this applies to you.

You will have an MRI or CT scan of your brain (if needed), chest, tummy (abdomen) and anywhere your cancer may have spread to

• Every 6 weeks during the first 6 months
• Every 9 weeks after this

This pattern may change slightly if you have the brain radiotherapy prophylactic cranial irradiation (PCI).

At 1 and 2 months after you finish the trial, you will see the doctor and have a blood test. At the first of these 2 visits you will also have a

• Heart trace
• Urine test
• Pregnancy test (if appropriate)

You then see the trial team every 3 months for up to 3 years after the last person started trial treatment. These visits will be at the same time as your routine appointments with your regular cancer doctor. You may also have blood tests and scans if your doctor thinks you need them. If you have started another treatment, the trial doctor may phone you at home instead to see how you are getting on.

Side effects

Common side effects of the trial treatments include

• Tiredness
• Feeling or being sick
• A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
• Fever and chills
• Dry skin, Rash, itching and flushing
• Stomach pain, heartburn, indigestion, loss of appetite, or feeling full
• Diarrhoea or constipation
• A reaction to the trial drug on the day you have it (infusion reaction), which may include a drop in blood pressure, chills, sweating and feeling and being sick – your nurse will watch closely for this
• Dry mouth, or strange taste in the mouth
• Heavy sweating and dehydration
• Wheezing, shortness of breath and cough
• Changes to your blood pressure
• Changes to your heart beat
• Headache, dizziness and weakness
• Hair loss
• Redness and swelling (inflammation) of the moist tissues that line the inside of your body openings (mucous membranes), for example your mouth
• Joint pain
• A strange squeezing feeling in your muscles (spasms)
• Numbness and tingling in your arms and legs
• Blood clots, usually in your legs (deep vein thrombosis or DVT) or lungs
• Nose bleeds, and bleeding in the upper part of your digestive system
• Swelling in the hands and feet (your ‘extremities’)
• Inflammation of the straps that hold your long bones together (your ‘tendons’)
• Forming of an abnormal connection between 2 parts of your bowel (colonic fistula)
• Increase in your blood sugar levels
• A drop in the levels of thyroid hormones, phosphate, magnesium and potassium
• Changes to the way your liver or gallbladder works

You can find out more about cisplatin and carboplatin chemotherapy on CancerHelp UK.