Melanoma Clinical Trial Summary
By: Keith Flaherty, M.D.
The University of Pennsylvania, Department of Oncology
While surgery is effective for the treatment of melanoma that has not spread beyond the skin, treatment for melanoma that has advanced beyond that stage is quite limited. Chemotherapy drugs and immune-stimulating drugs have a very limited ability to control, much less cure, advanced melanoma. For that reason, clinical trials that administer more cutting-edge therapies offer our best possibility of improving the treatment of melanoma.
Clinical trials are designated by their primary purpose. Phase I trials aim to determine the appropriate dose of a new therapy or the doses of two drugs when combined for the first time. Phase II trials are the first formal assessment of the benefit of a new treatment when people are treated in a uniform manner. Phase III trials compare a new therapy to a previously available or "standard" therapy to prove superiority.
With regard to patient access to clinical trials, phase III trials are typically the most restrictive in terms of the characteristics of the patients enrolled. Phase II trials can be as restrictive or, in some cases, less restrictive than phase III trials. Phase I trials tend to be the most inclusive of all trial types. The main factors that influence the ability to enroll on a clinical trial are: previous therapies for advanced melanoma, spread of melanoma to the brain, and overall health. All clinical trials restrict enrollment of patients who are very ill from their melanoma or other health problems. While exclusion from trials seems particularly unfair for patients whose melanoma is making them ill, the reason such rules exist that decades of cancer research has shown that people are very ill don't tolerate cancer therapies and don't receive the potential benefits. Some trials require that patients have no prior therapy for melanoma. This is typically not the case for phase I trials, which explains why patients who have not had success on a phase II or phase III trial frequently consider phase I trials.
Phase III trials require the largest number of patients and, therefore, enroll patients over a much longer period of time than other types of trials (2-3 years). Phase II and phase I trials typically enroll patients over a shorter period of time (12-18 months). The number of clinical trials in advanced melanoma available to consider at any one time will vary. In addition the availability of certain drugs will change depending on what phase of trial there are in.
There are a wide variety of therapies being evaluated currently, but most can be categorized as either immune enhancing therapies or tumor-targeted therapies.
Melanoma has always been considered a type of cancer which response better to immune therapies than other types. However, the two FDA approved therapies, interferon and interleukin-2, work in a small percentage of people. There have been some exciting breakthroughs in this area based on a more complete understanding of how melanoma is able to evade the immune system as it develops. Several new drugs have shown an ability to awaken immune cells that recognize melanomas as foreign. In patients with melanoma, these drugs have shown some ability to control advanced melanoma. Two challenges remain in this line of investigation: (1) in some patients immune cells also attack normal tissues, and (2) the percentage of patients who benefit form such therapy is not clearly superior to the currently available immunologic drugs. Nonetheless, trials with these drugs are clearly worthy of consideration.
In the area of tumor-directed therapy, several recent developments have energized the melanoma research community. Some of the critical abnormalities (mutations) that allow melanoma to form have recently been discovered. These mutations allow certain enzymes in melanoma cells to be overactivate and stimulate cell growth. Drugs that block some of these key enzymes have moved very quickly from the laboratory into clinical trials. Promising results from phase I and phase II trials suggest that this approach may significantly advance melanoma therapy. However, this approach is still being evaluated in phase III trials. These trials are clearly an attractive possibility for patients with advanced melanoma.
Currently, we remain limited to treatments with little evidence of benefit in this disease. Until a new therapy emerges from phase III trials and shows an impact on control of advanced melanoma, patients with advanced melanoma are urged to consider enrolling on clinical trials in order to gain access to the most promising therapies available.
