Early phase clinical trials are the first few times that a new experimental drug is tested on people. If a cancer treatment shows enough promise in the laboratory, then it might be decided to test it in people with cancer. Those who agree to join in Early Phase trials will be amongst the first patients in the world to receive the treatment, so there can be no promise of benefit, and no certainty of what the side effects might be.

Despite this, there are many patients who have taken part in Early Phase clinical trials knowing that they might not benefit themselves, but that some day, other patients might be helped.

The very first step is called a Phase 1 trial. The purpose of a Phase 1 Trial is to allow us to work out what dose and schedule of the drug should be used to treat patients:

• Usually, we treat between one and six patients with a given dose. Safety is paramount and therefore the first dose is always chosen with that in mind and side effects are monitored very carefully. As long as there are only a few and minor side effects, then we will increase the dose in another group of patients. We keep on raising the dose in this way, until eventually the side effects are such that any further increase would be unsafe.
• As we are keen to learn as much about the treatment drug as possible, blood and tissue samples (biopsies) are taken frequently, so that the levels of the drug in the bloodstream and cancer tissue are measured. We can also learn whether the treatment is having an effect on the target we have chosen in the tumour. In most cases, we also undertake a number of specialist scans, using new, highly technical imaging approaches, to monitor changes in the tumour.
• Patients participating in these studies need to be in good shape, despite their cancer, and have recovered completely from previous treatments. Taking part in a Phase 1 trial does mean spending a lot of time at the hospital having scans and treatment and the associated travelling time, which can be tiring, so they are not appropriate for all patients.
• Many patients have given their time in this way and have helped to develop the drugs which we now use on a routine basis.

The next step is a Phase 2 trial. Once the correct dose for the treatment has been found, another 20 to 40 patients are treated in a Phase 2 Trial. The aim here is to find out how many of those patients benefit, for example, by the cancer shrinking in size and this is balanced against any side effects which might occur.

Phase 3 and 4 trials test the effects of experimental treatments in hundreds if not thousands of people. They will often compare these potential treatments with the standard available drugs, before the new treatment is used routinely.

Unfortunately, not. We would like to include as many patients as we can, but to make the experimental treatments as safe as possible, there are rules about the kind of patients that can take part.

• Patients usually have to be well enough to be up and about for most of the day - and able to look after themselves.
• Your doctor will take blood tests to make sure that the trials would be safe for you.
• Your previous treatment for your cancer will be considered but this is not usually a barrier to experimental treatment.

The rules for each trial will be different e.g. some trials are specifically for patients with a certain type of cancer, such as breast cancer - but others are open to patients with any type of cancer.

The ECMC Network of 19 centres, located in NHS hospitals across the UK, work with cancer research charities, universities and pharmaceutical companies to test these experimental treatments in Early Phase trials.

We have teams of doctors, nurses, pharmacists and laboratory scientists who specialise in the care of patients who volunteer for early clinical trials. They have access to many experimental treatments, and new trials start regularly. On the CancerHelp UK website, you can find lists of both the Early Phase trials being performed in all the ECMC Centres and also the trials being performed in your local Centre. You can also search these trials by specific cancer type.

Researchers at The Institute of Cancer Research have carried out Phase 1 and 2 trials in men with advanced aggressive prostate cancer that had progressed despite treatment with most, if not all, available drugs for this disease. These patients took part in a trials involving treatment with a new drug called Abiraterone which was discovered and made by chemists at The Institute of Cancer Research in Sutton.

Prostate tumours need testosterone (a hormone) to survive and grow, and recent studies suggest that prostate cancer cells produce their own hormones to enable the tumour to carry on growing. Abiraterone has been designed to work by stopping the cancer cells (and cells in the adrenal gland) from producing the hormones they need to keep growing.

The Institute scientists began developing Abiraterone in their laboratories over 15 years ago and worked with the Drug Development Office at Cancer Research Campaign (now Cancer Research UK) to produce it in a form that could safely be taken by patients. They then carried out a preliminary clinical trial of Abiraterone in men with prostate cancer giving patients a maximum of 12 days of drug to show that the drug had its desired hormonal effects.

The patients were given one tablet a day and blood samples were taken to find out whether the drug was being absorbed, where in the body it was travelling to and how it was being broken down. The blood tests also measured the levels of testosterone in the patients to see whether the drug had reduced the amount of hormone produced by the tumour.

This initial trial showed that Abiraterone decreased the level of testosterone production in most of the patients. Subsequently researchers at The Institute began working with a company called Cougar Biotechnology, to develop the drug further and set up more trials.

A Phase 1/2 trial, led by Dr. Johann de Bono at The Institute of Cancer Research (ICR), was set up to find out if the drug worked to control prostate cancer growth. 54 men with advanced prostate cancer took part in the trial. They received a continuous dose of Abiraterone (once daily) which was found to be very well-tolerated by most patients. In many cases, the tumour shrunk in size with up to three quarters of men having evidence of benefit, frequently being able to reduce the amount of pain-relieving drugs they were taking.

A number of important laboratory studies were conducted at the same time; these were supported by the ECMC Initiative, and were aimed at understanding which patients were most likely to benefit from Abiraterone. In one study, researchers at the ICR looked at circulating cancer cells in the blood of the patients as a way of gaining a better understanding of how the drug was working in the body. They found that treatment with Abiraterone substantially reduced the number of circulating tumour cells. This is an example of how the scientists and health professionals at the ICR work closely together to make sure that drug development and clinical research is as safe and efficient as possible.

Men with late stage advanced prostate cancer are not expected to live more than 18 months after undergoing standard treatment so the use of Abiraterone is an exciting development that could potentially benefit thousands of men each year. An international phase 3 trial involving 1,200 patients is now underway and if this shows that Abiraterone is safe and effective, the drug may be available to patients as early as 2011.

Professor Stan Kaye, Institute of Cancer Research