Clinical Trials

What is a clinical trial?

During various stages of the patient pathway, patients or parents/ carers may be asked to take part in a form of medical research called clinical trials, which helps doctors to improve existing ways or find new methods to prevent, diagnose and treat disease.

Medical research, such as looking for a new drug treatment usually starts in the laboratory. If the results of these laboratory studies look promising, there comes a point where the treatment needs to be examined for its effects on the people who will receive it.

Clinical trials are part of a long cancer research process and are used to test how well new drugs, changes to existing treatments, combinations of treatments, radiotherapy, surgical techniques or totally new methods, such as gene therapy or immunotherapy work in people. There are also types of trials that look at quality of life or supportive care issues.

To be certain the treatment or drug is safe and effective, it has to go through a lot of testing to discover,

• The safest and most effective (therapeutic) dose,
• What the side effects are (toxicity),
• If the drug/ treatment works better than existing treatment,
• How much it benefits the patient (outcome).

The testing is carried out in stages known as phases. As the treatment goes through these phases it will be examined using more people than the previous phase and on more specific types of cancer.

There are generally three phases of clinical trials for a treatment to go through before it can be licensed. However, a fourth phase sometimes looks at the long term effects and side effects previously not reported or observed for licensed drugs, treatments or diagnostic procedures.

Many drugs or treatments may not make it past phase 1 and some may make it to phase 3 but the benefit to the patient may not be as much as first thought.

Phases of clinical trials

Phase 1: If a drug looks promising in laboratory studies, a phase 1 trial may be carried out. This is usually the first time a new drug is tried in people. These types of trials do not usually look at the effect on specific types of cancer but look at things such as side effects and the safest and most effective dose. These types of trials are usually done with a small number of people, usually 10-30.

Phase 2: This type of trial may be open to people with specific types of cancer or a number of different cancers. They are usually carried out on more patients than phase I trials, usually around 100; mainly to look at, which type of cancer the drug works best against, to look at the best dose and side effects again, and to find out if the drug is worth taking to a much larger phase 3 trial.

Phase 3: If a drug in a phase 2 trial looks as if it works as well or better than an existing treatment, a phase 3 trial is carried out. These trials are usually open to people with a specific type of cancer. Many more people are included in these trials, this helps to make sure doctors can see how well the drug may or may not help.

A single phase 3 trial can be carried out in hospitals in many countries, known as an International clinical trial.

How do trials examine whether the new treatment is better than the existing one?

The new drug or treatment is usually compared to an existing treatment. Patients will be put into one of at least two groups. For example, either the ‘new drug group’ or the ‘existing treatment group.’ This is done randomly by a computer.

Randomisation reduces bias and also helps doctors to be certain that it was the drug that caused the effect and it did not just happen by chance.

You may see the terms ‘blind’ or ‘double blind’ randomised clinical trial. A blind trial means the patient does not know if they are receiving the existing treatment or the new one. In a double blind trial neither the doctors nor the patients know which treatment they have received.

How to get on to a clinical trial and where to find clinical trials?

The consultant oncologist or surgeon in charge of treating individual patients will be aware of national or international trials and may suggest or inform patients/ parents of open and recruiting clinical trials. However, not all patients may be suitable for particular trials. There may be some trials that consultants are unaware of and it is possible for patients and parents to find smaller clinical trials or those taking place locally.

BCRT is compiling a list of open and recruiting clinical trials for ‘primary bone cancers’.

Cancer Research UK also has a database of ‘cancer-related’ clinical trials, here.

The largest searchable database of ‘cancer-related’ clinical trials is operated by the National Cancer Institute (USA).

Clinical trials may not always be available, and the patient may not meet some of the requirements to be treated on trials that are available. If a clinical trial is suggested by the doctor, they will speak to the patient about the trial and/ or give them information to read.

Doctors will describe what taking part in the trial will mean for the patient, what happens before and during the trial and about possible risks. Patients will be given time to think about whether they wish to take part in the trial.

If patients/ parents find a trial, they should discuss it with their consultants. There are lots of things that need to be considered before a patient can take part in a trial. Some of these considerations or ‘eligibility criteria’ are known as ‘inclusion’ and ‘exclusion’ criteria and they will be fully explained to patients.

These criteria are like guidelines detailing who can and cannot take part in the trial. For example, inclusion and exclusion criteria may depend on

• Age,
• Gender,
• Medical history,
• Current health status,
• Types of treatments already given,
• Type of cancer,
• Newly diagnosed/ recurrent cancer,
• Stage of cancer.

If the people taking part in a clinical trial have too many differences between them, it may be difficult to obtain reliable accurate results and whether it was the treatment being tested that actually made a difference.

Deciding whether to take part in a clinical trial

As part of making a decision, patients or parents may want to think about the benefits and risks involved in taking part in a clinical trial. Benefits may be that parents and patients will have an active role in his or her health care, may have access to new treatments before they become generally available, and helping others by contributing to medical research.

Risks could include side effects of the drug, which may be unpleasant, or the treatment may not be safe or effective for the patient. The trial may involve frequent stays in hospital and extra cost. Upon contacting a trial coordinator, it may be helpful to have a list of questions written down.

Patients/ parents should not feel that any question is a daft or stupid question. Doctors will be happy to answer any questions patients/ parents may have about clinical trials.

As well as having questions written down, it is also a good idea to write down the answers or better still ask the doctor whether you can record the answers on a voice recording device. That way people can listen to or read the answers to questions at a time when there may not be so much information to take in all at once. Having a family member there may also help.

Examples of on-going International clinical trials for primary bone cancers

Two examples of International clinical trials looking at treatments for primary bone cancers are EURO-E.W.I.N.G.99 (Ewing’s sarcoma) and EURAMOS-1 (osteosarcoma).

EURO-E.W.I.N.G.99

An ongoing randomised international trial known as EURO-E.W.I.N.G.99 is aiming to improve disease outcome (survival) in patients with Ewing tumours. Its main aim is to increase survival by improving the response to chemotherapy by an increase in its intensity without increasing toxicity (side effects).

EURAMOS-1

A large clinical trial by the European and American Osteosarcoma Study (EURAMOS) called EURAMOS-1 is in progress in patients with tumours that can be surgically removed, to find out if treatment and disease outcome (survival) can be improved.

In this study, patients are divided into two groups based on response to chemotherapy. Patients’ response to chemotherapy is worked out by using a microscope to check the amount of cells that have been killed by the chemotherapy given before surgery. Response is considered either ‘good’ or ‘poor’ based on the number (percentage) of cells that have died.

Patients that respond well to pre-surgery chemotherapy are split into two groups randomly. One group will be given

Methotrexate,
Doxorubicin and
Cisplatin.

The other group will also receive the three chemotherapy drugs along with a further drug called alpha-interferon. The aim of this is to see if adding this drug can help prevent the cancer returning.

Patients that respond poorly will also be split into two groups randomly. One group carries on with the 3-drug combination chemotherapy.

The other group receives the three drugs along with two other chemotherapy drugs called ifosfamide and etoposide. These two drugs are currently used to treat osteosarcoma that has returned (recurrent).

A list of clinical trials involving primary bone cancers will be available soon.