Types of trials

New cancer drugs are usually tested using the following process. Drugs are tested in the laboratory and if it seems that they may be helpful in the treatment of a particular cancer they are tested in phase 1 trials. If these are successful the drug is entered into phase 2 trials and then phase 3.

Phase 1

Phase 1 trials of new cancer treatments use drugs that have been tested on cancer cells in the laboratory and have had an effect. Phase 1 is the first stage in which the drugs are used to treat patients. These studies have small numbers of patients. Phase 1 drugs are offered to people whose cancer has come back or spread and there is no other standard treatment that may help them. It is not expected that the treatment will cure the cancer; rather, the trial aims to find out:

• how much of the treatment can be given without causing serious side effects
• which side effects the drug causes
• whether the drug has any effect on the cancer.

In a phase 1 trial, the first group of 3-6 patients are given a small dose that is expected to be safe. If none of the patients has any side effects the next group of patients will be given a higher dose. In this way the dose of the drug is increased until some people do have side effects. When side effects are seen that make it unsafe to increase the dose further it is known as the maximum tolerated dose and the dose is not increased any more.

However, it is impossible to predict whether a new treatment will cause harmful side effects in people, and patients in this type of trial need to be monitored carefully. Phase 1 trials are usually carried out in clinical research units at specialist hospitals, rather than in local hospitals, and this may involve a lot of travelling to and from the hospital.

If the drug has an effect on the cancer, and a safe dose has been found, the drug will then be tested in phase 2 trials.

Phase 2

By the time a treatment reaches phase 2, researchers will know quite a lot about it. The phase 1 trials will have shown what most of the major side effects are and whether the drug actually has some effect on particular types of cancer. The aim of phase 2 trials is to look at how many people the treatment is effective for and which types of cancer it might be used to treat. Researchers will know which side effects are likely to occur so that they can deal with these straight away if necessary.

Phase 2 studies have more patients, perhaps a few dozen. These patients will be closely monitored to see whether their cancer is getting smaller. If the cancer does shrink, it is known as a response to the treatment. The trial will also look at any side effects caused by the treatment. Sometimes phase 2 studies include different ways of giving the new treatment; for example, patients may be given the same drug by injection, or as tablets. These trials may be randomised.

Phase 3

These studies follow phase 2 and the main aim is to compare the effectiveness and safety of the treatment being tested with current treatments and to gain more information about the side effects that the treatment may cause. It is hoped that one of the treatments will be found to be more effective, although it may be just as useful to find that they are all equally effective but one has fewer side effects. Phase 3 trials are large and may include hundreds, or sometimes thousands, of patients from many different hospitals, often from several countries. Researchers measure various aspects, such as whether the growth of the cancer slows, and, in the longer term, how long patients remain free of cancer. Researchers may also measure how the treatment affects patients’ quality of life. Phase 3 trials always involve randomisation.

Overviews and meta-analyses

These are analyses that bring together the results of a large number of similar studies. In doing this, doctors and researchers can try to get more accurate answers than from individual trials. They may help to clarify the true value of a treatment and they may also help to identify other important questions that need to be answered. Overviews and meta-analyses do not involve more patients: they analyse the information gained from previous trials.