This is the seventh and last part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article delves into the role of clinical trials and questions to ask your doctor.

There are different types of clinical trials, looking into screening or diagnosis for instance. The trials that are sometimes of most interest to people already diagnosed with cancer are trials that test new treatments.

Phases of Clinical Trials

A new treatment must go through several phases of clinical trials to prove that it works better than existing treatment and can be adopted into routine care. A potential treatment will only move on to the next phase of research if it is safe and shows promise.

Phase 0 and I Trials

The earliest-phase trials are Phase 0 and Phase I. These are usually very small trials, involving 10–50 people. Their aim is to find out if a potential new treatment is safe, what the side effects are, and what happens to the treatment in the body (how your body gets rid of a drug, for example). Researchers may include a number of different cancer types in these early-phase trials.

Phase II Trials

Once a treatment is found to be relatively safe, a Phase II trial may take place. This is a medium-sized trial, usually of fewer than 100 people. Phase II trials usually focus on one or two cancer types that the treatment worked best for in earlier trials.

The aim of Phase II trials is to find out more about side effects and see how well a treatment works for specific types of cancer. Sometimes Phase II trials are randomized, but generally not (there is more about randomization in the section below on Phase III trials).

Phase III Trials

Phase III is the largest phase of a clinical trial and is most likely what people think of when they think about research. The aim is to test a new treatment against a treatment that is already in use to see which works better for a particular type and stage of cancer. But Phase III trials also collect more side-effect data and look at the quality of life of those having each treatment.

Usually, hundreds or even thousands of people take part in a Phase III trial, and they are often international. These trials are usually randomized. Randomized means that participants are put into two or more groups to compare the existing treatment and the new treatment. The groups have to be as similar as possible. You can’t choose which group you’re in, because that could affect the results.

Participants in Phase III trials are monitored by the researchers for a number of years afterwards. This is to see how well each treatment works in the long term – whether it stops an early cancer coming back or controls an advanced cancer for longer. Phase III trials often take several years to show a result.

Phase IV Trials

Phase IV trials are often referred to as ‘post-marketing studies’, and are conducted after a treatment is approved. These trials provide additional information on the treatment, including risks, benefits, and best use.

The Benefits and Risks of Taking Part in a Trial

A common reason people have for entering a clinical trial is that it may give them access to an experimental treatment. Many people also feel that they are giving something back and that by taking part they can help people with cancer in the future.

Remember, if you enter a randomized trial, you may or may not get the experimental treatment. You may not know which treatment you’re getting, as many randomized trials are ‘blinded’. Blinded means the doctors and researchers running the trial don’t know who is having which treatment. This information is kept secret (‘blinded’) until it’s time to analyze the results.

With any experimental treatment, there is no absolute guarantee of safety. Treatments are tested thoroughly before they are given to people. With each phase of research, more is learned about possible side effects. But the treatment won’t have been given to large numbers of people, and not all side effects may be fully known.

As well as treatment, trials can often mean that you have more tests and scans than usual. Some people feel this is a benefit – they are having more check-ups and so feel reassured. Others find it stressful. There may be travel involved too, back and forth to the treatment center, though some costs may be covered by the organizer of the trial. It’s worth thinking about the time commitment too, and the impact more tests may have on your well-being before you join a trial.

Trials often have very strict entry (eligibility) criteria. This is so they can make accurate comparisons between groups of participants.

You will only be able to enter trials that are suitable for you. Suitable trials are those looking into treatment for your type and stage of cancer. There may also be restrictions on entry for treatments you’ve had in the past or other medical conditions you might have.

You have to give your formal consent to take part in a trial. Before you sign, the researchers have a legal obligation to tell you about:

• the trial aims
• the treatments
• the potential benefits and risks, including side effects
• the tests and check-ups you’ll need
• how long you’ll have to come for follow-up appointments
• whether they will be keeping tissue or blood samples for future research.

They’ll give you a patient information sheet to take away with you, with all of this information written down.

You don’t have to decide immediately whether you’ll join or not. It’s important to say if you’d like some time to think it over, and maybe talk things over with those closest to you. Ask if there’s a number you can call if you have further questions about participating.

Please don’t feel obliged to enter a trial. If you don’t, your doctor won’t be offended or upset, and it won’t affect your current treatment. And it’s important to know that you can withdraw from (leave) a trial whenever you want. You don’t have to give a reason.

How to Find Out about Clinical Trials

The easiest way to find out about clinical trials is to ask your own specialist. They have access to all of your test results and past treatments, so they can tell you which trials are suitable for you (and which you are likely to be eligible for).

Depending on where you live, you may also be able to find clinical trials online. There are cancer clinical trials databases based in the UK, Europe, and the USA.

The US National Library of Medicine (NLM) runs a clinical trials database that has information on trials running worldwide. It isn’t written for patients, so it can be difficult to understand. But you can search specifically for NSCLC trials and by country.

The European Union Drug Regulating Authorities Clinical Trials Database is the European database for all interventional clinical trials on medicinal products taking place in the European Union/European Economic Area. Again, this isn’t written for the public, so it can be difficult to read.

Cancer Research UK has a clinical trials database that is written specifically for the public, in plain English. It only lists trials that are active in the UK (but of course this does include some international trials). You can search for NSCLC trials, by trial phase, and for trials in England, Scotland, Wales, or Northern Ireland.

What to Ask about a Clinical Trial

If you are considering taking part in a clinical trial, it may be helpful to think through what you’d like to know before you join.

As well as finding out about the trial aims and treatments, there are practical concerns, such as how much time you’ll need to spend having tests, treatment, and check-ups. There may be hidden costs, such as parking and hotel stays. Ask if any financial support is available to help with these.

Questions for Your Doctor about Clinical Trials

• Are there any trials I could enter that are for my type and stage of cancer?
• What treatment can you offer if I decide not to enter a trial?
• What do the researchers hope to find out from this trial?
• What are the possible advantages and risks of taking part?
• Is the trial randomized?
• What will I have to do if I join the trial, including tests and check-ups?
• Can I have tests and treatment at my usual treatment center or will I have to travel?
• Is there any help available to cover costs?
• Will joining a trial mean that there are any medicines or treatments I can’t have?
• Is the trial insured?
• Will taking part in a trial affect my medical insurance?

Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).