Clinical trials are typically conducted in different phases. Each phase is designed to answer certain questions. Knowing the phase of the clinical trial is important because it can give you some idea about how much is known about the treatment being studied. There are advantages and disadvantages of taking part in each of the different phases of a clinical trial.
Clinical trials for mesothelioma cancer passes through this different stages:
1-Phase 0 clinical trials: Does the new drug work? How does it work?
Phase 0 studies are exploratory studies that involves the use of few small doses of a new drug in each patient. They test to find out whether the drug reaches the tumor, how the drug acts in the human body, and how cancer cells respond to the drug. The patients in these studies must have extra biopsies, scans, and blood samples. The biggest difference between phase 0 and the later phases of clinical trials is that there is no chance of a direct benefit to the patient from taking part in a phase 0 trial. Because drug doses are low, the chances of risks is less compared to the other phases of the clinical trial.
Phase 0 studies help researchers find out early which drugs do not do what they are expected to do. If there are problems with the way the drug is absorbed or acts in the body, this should become clear very quickly in a phase 0 trial. This process may help avoid the delay and expense of finding out years later in phase II or even phase III clinical trials that the drug doesn’t act as it was expected to based on lab studies.
The studies are very small, mostly with fewer than 20 people. Although this phase 0 is not a compulsory part of testing a new drug, it is used as part of an effort to speed up and streamline the process of testing new drugs.
2-Phase I clinical trials: How safe is the new treatment?
Although the treatment has been tested in lab and animal studies, the side effects in people can’t always be predicted. For this reason, these studies usually include a small number of people (15 to 50). These studies are usually done in major cancer centers.
The main reasons for doing phase I studies are to find out the highest dose of the new treatment that can be given safely (without serious side effects) and to decide on the best way to give the new treatment. The first few people in the study often get a low dose of the treatment and are watched very closely. If there are only minor side effects, the next few patients may get a higher dose. This process continues until doctors find the dose that is most likely to work while having an acceptable level of side effects.
Safety is the main concern at this point because this is usually the first time the treatment has been used in people. Doctors keep a close eye on how the people in the study are doing. They watch for any common but serious side effects. Special tests, such as blood tests to measure levels of the drug in the body at certain time points, are often a part of these clinical trials. Some studies may require time in a hospital.
These studies are not designed to find out if the new treatment works against cancer. Overall, these trials are the ones with the most potential risk. And only phase 0 has a smaller chance of helping you than phase I. But phase I studies do help some patients. For those with life-threatening illnesses like mesothelioma, weighing the potential risks and benefits carefully is needed.
3-Phase II clinical trials: How effective is the new treatment?
If a new treatment is found to be reasonably safe in phase I clinical trials, the treatment can then be tested in a phase II clinical trial to see if it works the way researchers think it will.
Usually, a group of 25 to 100 patients with mesothelioma cancer gets the new treatment in a phase II study. They are treated using the dose and method found to be most safe and effective in phase I studies. In a typical phase II clinical trial, all the volunteers usually get the same dose, and no placebo is used.
But some phase II studies do randomly assign participants to 1 of 2 treatment groups, much like what is done in phase III trials (see below). These groups may get different doses or get the treatment in different ways to see which provides the best balance of safety and effectiveness. Phase II studies are often done at major cancer centers, but may also be done in community hospitals or even doctors’ offices.
Doctors look for some evidence that the treatment works. The type of benefit or response they look for depends on the goals of the clinical trial. This may mean the tumor shrinks or disappears. Or it might mean there is an extended period of time where the tumor does not get any bigger, or there is a longer time before a cancer comes back. In some studies the benefit may be an improved quality of life. Many studies look to see if people getting the new treatment live longer than they would have been expected to without the treatment.
If a certain percentage of the patients benefit from the treatment, and the side effects aren’t too bad, the treatment is allowed to go on to a phase III clinical trial. Along with watching for responses, the research team keeps looking for any side effects. Larger numbers of patients get the treatment in phase II studies, so there is a better chance that less common side effects may be seen.
4-Phase III clinical trials: Is it better than what’s already available?
Treatments that have been shown to work in phase II studies usually must go through one more stage of testing before they are approved for general use. Phase III clinical trials compare the safety and effectiveness of the new treatment against the current standard treatment.
Phase III clinical trials usually have a large number of patients, at least several hundred. These studies are often done in many places across the country (or even around the world) at the same time. They are more likely to be offered by community-based oncologists.
Because doctors do not yet know which treatment is better, patients are often chosen at random, (called randomized) to get either the standard treatment or the new treatment. When possible, neither the doctor nor the patient knows which of the treatments the patient is getting. This type of study is called a double-blind study.
As with other studies, patients in phase III clinical trials are watched closely for side effects, and treatment is stopped if they are too bad.
Randomization is used in many phase III studies because it helps reduce the risk that one group will be different from the other when they go into the study, which could affect outcome. Blinding reduces the risk that the doctors will be biased in their evaluations of the patients’ outcomes. These controls help make the study results more credible.
5-Phase IV clinical trials: What else is there to know about the drug?
Although a drug might have been approved for general usage, the full effects of the treatment may not be known, and their might still be some questions about the drug that are yet to be answered. For example, a drug may approved by the relevant drug regulatory authority based on the fact that it was shown to reduce the risk of cancer recurrence but does this mean that those who get it are more likely to live longer? Are there rare side effects that haven’t been seen yet, or side effects that only show up after the drug is used for a long time? These types of questions may take many years to answer fully, and may not be critical for getting a medicine to market. They are often addressed in what are known as phase IV clinical trials.
Phase IV studies look at drugs that have already been approved by the relevant drug regulatory bodies. They are already available for doctors to give to patients, but these studies are still needed to answer important questions.
When thinking about taking part in a phase IV trial, you should know that the drug has already been approved for use. The care you would get in these types of studies often is very much like what you could expect if you were to get the treatment outside of a clinical trial. You should be reassured that in taking part you would be getting a form of treatment that has already passed through different phases of testing and that you would be doing a service to future patients.