Clinical Trials Phases

A new drug or other treatment goes through several different phases of clinical trials prior to FDA (Food and Drug Administration) approval.

Investigational New Drug Application (IND)
If the clinical trial is to evaluate a new drug, the first step is an action plan called the Investigational New Drug Application (IND) that is presented to the FDA. This application contains everything known about the therapy, including all the data from laboratory and animal tests. If the FDA feels that the therapy might possibly benefit people, it approves the IND and the first clinical trials can begin.

Phase I Trials
These first studies in people evaluate how a new treatment should be administered (orally, intravenously, by injection, inhalation, etc.), how often, and in what dosage. The primary objective of a Phase I trial is to define the proper dosing and identify side effects. A Phase I trial usually enrolls only a small number of patients.

Phase II Trials
A Phase II trial provides preliminary information about how well the new treatment works and generates more information about safety and benefit. Phase II studies may focus on a particular type of cancer or on general types such as solid tumors.

Phase III Trials
These trials compare a promising new drug, combination of drugs, or procedure with the current standard therapy. Phase III trials typically involve large numbers of patients from doctors’ offices, clinics, and cancer centers nationwide. The reason that the Phase III clinical trial has been initiated is that the superiority of one treatment over the other has not yet been firmly established.

If you participate in a Phase III treatment trial, you are likely to be randomized (assigned by chance) to a group receiving either the new intervention or the standard intervention. Neither you nor your physician choose whether you get the new intervention or the standard treatment.

Trials designed in this way are also called randomized controlled trials. If you are assigned the standard intervention, you receive what experts view as the best treatment available. Experts believe that each treatment is effective, but really don’t know which one is better. If you are assigned the new intervention, you receive a treatment that some experts think may have some advantages over the standard.

Phase IV Trials
Some use the term Phase IV to include the continuing evaluation that takes place after FDA approval, when the drug or treatment procedure is already on the market and available for general use. This is also called a postmarketing surveillance study.

Becoming Part of a Clinical Trial
Most oncologists (cancer doctors), especially those that specialize in the treatment of mesothelioma, will most likely be aware of the clinical trials that are currently seeking patients who are fighting mesothelioma.

If you are a candidate, you should know that there are basically 4 types of clinical trials.
• Treatment trials - these trials test new approaches to cancer treatment, be it a drug, radiation therapy, a multi-modal therapy, or a totally new treatment procedure.
• Prevention trials - these trials test approaches to lowering the risk of developing a certain kind of cancer.
• Screening trials - such trials test new ways to detect cancer, particularly in its early stages. These are important trials in the field of mesothelioma, which is usually diagnosed in its late stages.
• Supportive care trials - these trials test ways to improve comfort and quality of life for cancer patients, often referred to as palliative treatments.

Patients can be involved in various phases of a trial.
• Phase I helps determine how a new drug should be given and attempts to measure safe dosage. This phase generally involves only a handful of volunteers.
• Phase II trials usually focus on one particular type of cancer and are used to test the safety of the drug and how well it works in combating a particular cancer.
• Phase III trials test new drugs or treatments in comparison with the current standard. In a process called randomization, the participant will be assigned to the standard group or the new group. Phase III trials are the largest and may often involve doctors and hospitals throughout the country.

Once a product has successfully completed Phase I and II trials, the sponsor (usually a pharmaceutical company) files a New Drug Application (NDA) with the FDA. In this application, the sponsor requests permission to begin Phase III trials with the anticipation that the product will, at the completion of Phase III trials, show enough benefit both in safety (equal or improved quality of life compared to standard care) and efficacy (equal or greater reduction in tumor growth and extended life compared to standard treatment).

Every product for mesothelioma treatment that goes through review by the FDA has all the data for the studies examined by a committee comprised of leading oncologists from the around the United States. The committee also includes a mesothelioma survivor who brings the special patient/survivor perspective to the discussions.

Phase I trials are often called dose escalation trials because each group or cohort of patients in the study is given a higher dose than the last. This is done to establish an upper safe limit or threshold for the treatment and monitor for side-effects. There are usually at least three patients in a cohort to ensure that observed effects are repeatable and not reflective of one individual's unusual biology.

Phase II trials are given to larger groups of patients to establish if the treatment has an effect and to further monitor for safety.

Phase III trials are given to an even larger group of patients to confirm the treatment's effectiveness, monitor for side effects, compare it to existing treatments, and to collect information to allow the experimental drug or treatment to be used safely.

There is also a rarely discussed phase IV clinical trial which is done after the release of a treatment. This is done to continue to monitor for effectiveness, refine the target population for the treatment, and to monitor for safety.
Not all clinical trials are for treatment purposes. There are trials for evaluating preventative measures, to assess diagnostic tools or techniques, to evaluate screening methods for cancer, and to assess quality of life protocols.

Approval by the FDA generally means that insurance companies will pay for the treatment.
Once a product is approved by the FDA, it may be used by a physician in any way he or she feels it will be beneficial. A therapy approved for breast cancer, for example, may still be in clinical trials for mesothelioma but enough data is available so that your physician feels this therapy might benefit you. Your doctor could suggest to you that he or she treat you with that therapy.

However, some insurance companies will not pay for the use of a therapy that is not approved by the FDA for that particular disease. This is called “unapproved use” or “unapproved indications.” A therapy for breast cancer might not be paid for when it is used to treat mesothelioma. However, many cancer advocates and groups are working to ensure that these “unapproved uses” are paid for.

Some supportive care, prevention, and screening trials are not done in phases. These trials compare groups of people using a certain anticancer strategy (counseling, behavior change, detection method) with groups that do not receive the test strategy.