What is a Clinical Trial?
Clinical trials are research studies that usually test a new approach to therapy. There are several different ways that trials are designed, but most fall into one of three categories: Phase I, II, or III. Phase III clinical trials focus on a particular disease and ask specific scientific questions which have the long-term goal of defining the best approach to therapy by comparing one therapy to another.
Phase I trials define the initial safety and toxicity of a new drug. In phase I studies the drug is given at a dose expected to be safe based on adult human and/or animal studies to the initial patients and then subsequent patients are given increasing doses of the drug. The dose is increased carefully, usually in 3 patients before going to the next higher dose. In this manner the maximal dose that can be tolerated by patients is defined and can then be used in a larger number of patients to study the anti-tumor activity of the drug in a phase II study.
Phase II trials test the anti-tumor activity of new approaches in which a safe dose has been established in a phase I study. In a phase II trial, a new drug is often used at the maximal tolerated dose that was defined in a phase I study. A number of patients with neuroblastoma are treated with the new drug to determine what portion of tumors respond and for how long and to further define side effects (toxicity).
Phase III trials are large studies that definitively and scientifically test a new treatment in comparison to the current standard treatment to determine if the new approach improves outcome. After agreeing to participate, patients are assigned to new or standard therapy by chance (randomized assignment). Patients who cannot participate in a phase III clinical trial should receive therapy that has been proven in previous clinical trials to be safe and to provide the best chance of achieving long-term survival.
Why Participate in a Clinical Trial?
An advantage to participating in a clinical trial is that the patient receives a therapeutic approach that has been mapped out and reviewed by a team of investigators who specialize in the disease being studied. Therapy given outside of the context of a clinical trial is at the discretion of the treating physician and may not be reviewed by experts in a particular disease. For many illnesses there is an accepted treatment that has been shown through the clinical trials process to be the standard of care for that disease -- meaning it is safe and effective. Unfortunately in cancer, and especially high-risk neuroblastoma, we do not have a standard treatment that is highly effective for essentially all patients. Participation in clinical trials allows patients access to state-of-the-art treatment and to also have the possibility of being among the first to benefit from a new and more effective treatment.
How are Clinical Trials Designed and Reviewed?
The larger the organization carrying out the trial, the greater the review of the plan of therapy. For example, a cooperative group or consortium trial that involves multiple hospitals and research centers would be developed and reviewed by many pediatric oncologists, surgeons, pathologists, radiation oncologists, nurses, statisticians, and patient advocates in the organization, as well as by the National Cancer Institute's Cancer Treatment Evaluation Program (CTEP), and by Institutional Review Boards (IRBs) responsible for protection of human subjects enrolling in clinical trials. IRB review ensures that the rights of the patient will be upheld and protected and that the patient will not be exposed to any unnecessary or extreme risk if he/she agrees to participate in the clinical trial.
The reviews of clinical trials in high-risk neuroblastoma address a number of questions, including :
1. Based on pre-clinical and clinical data, is the therapy to be tested in the trial likely to be effective against the disease?
2. Is the risk of serious toxicity during therapy appropriately balanced by the potential benefit to the patient?
3. What is known about the risks of long-term complications (called "late effects")? Examples of such risks include decreased intellectual ability, impaired growth and development, increased risk of cancers other than neuroblastoma, and hearing loss. In the case of a new therapy, these risks may be relatively unknown compared to standard therapy. When there are data to suggest approaches to minimize such risks (without adding other risks, such as therapy failure), does the clinical trial employ such approaches?
4. Is the option of being treated with a known standard therapy available to those patients who choose not to enter onto the clinical trial?
The above questions are appropriate for parents to address with their oncologist when evaluating any therapeutic approach for neuroblastoma.