What are clinical trials? Clinical trials have been established as one of the most important tools that can lead to improved treatment of cancer patients. Before a new drug or treatment program can be approved for use in a specific disease in the United States, data must be presented to the Federal Drug Administration (FDA) that it is effective in treating a specific disease and that it is safe in terms of its toxicity, side effects, and interactions with other medications. To establish these claims, all new drugs and treatments must go through vigorous testing. Most new drugs are first tested in the laboratory against a wide range of cancer cells and then in mice bearing human tumors. These pre-clinical studies determine whether there is potential usefulness for the new agent. Only about 1 in 1,000 tested compounds will be considered for clinical trials in humans.

In a carefully designed and monitored stepwise manner, the tolerance of a new agent will be tested in a group of volunteers who may have a wide variety of advanced cancers. This Phase I trial will be performed only after the proposed study has been carefully examined by an Institutional Review Board at a hospital or university where the trial is to be performed. This Board is made up of experts in the field, clergy, ethicists, and patient advocates. In a Phase I trial the toxicity of the new compound will be assessed. The effect of the new compound on the blood counts, on the GI tract, on blood pressure, on heart and lung functions and other systems, are all very carefully followed. The dose of the compound is slowly elevated until the maximum tolerated dose has been determined. This is not a trivial exercise and can be performed only in institutions where well-trained staff are available to carefully monitor every patient. While it is not the intention or design of the Phase I clinical trial to study the tumor response to the drug, this is always recorded as well for advanced information as to which new agents might have some effect on the particular tumor which the volunteer may have. At the completion of a Phase I trial, the dose of the new medication that can be safely administered will have been determined.

After the toxicity of the new agent has been established, it will be used in studies to evaluate its efficacy against a wide spectrum of different cancers in a Phase II trial. In this trial, data from the laboratory pre-clinical studies as well as the Phase I study are utilized so that patients with specific types of cancer and specific extent of disease are especially recruited. The maximum tolerated dose of the new agent, determined in the Phase I studies, is then given to see how effective it is in destroying the measurable disease in these patients. In a Phase II trial there is considerable likelihood that patients will be helped by the new treatments. This is true, particularly in late Phase II trials. Based upon previous Phase I and Phase II studies results, there is a reasonable chance that the patients will receive a benefit from new drugs which will not be available to the general public for a number of years. By volunteering for a Phase II trial there is the potential that a patient will receive an advanced treatment which may become standard treatment some years ahead.

After carefully assessing responses and re-evaluation of toxicity, a new agent may then find its way into a Phase III trial. Phase III trials are generally randomized so that patients with a specific tumor, specific site, and a specific extent of disease will either receive the best standard treatment available or will receive the new experimental treatment. As the trial progresses and as the data reveals that one treatment arm is statistically significantly better than another, the trial must be closed and the patients receiving the inferior treatment will be offered the superior treatment in the other arm. These trials are carefully monitored and reviewed periodically by the Institutional Review Boards, statisticians, the National Cancer Institute and other sponsoring organizations. On the basis of the conclusions of a Phase III trial, data will then be submitted to the FDA so that the new agents could become approved for the specific cancers involved. In many cases it becomes the standard of care for future patients.

The entire drug discovery program from the initial laboratory study to the conclusion of Phase III clinical trials and approval by the FDA may take as long as 10 years. By participating in a clinical trial, patients stand to benefit by receiving newer, more effective treatments years earlier than they would become available to the general population. It should be pointed out that when a new agent is combined with an already-established treatment, it must be submitted to the rigors of a clinical trial before it becomes standard treatment for the future.

Thus, in this carefully monitored sequence, from studies of toxicity to studies of efficacy to randomized trials of improved outcomes over standard treatment, we have accumulated sound scientific evidence to make judgments of the value of new cancer treatments. Information from clinical trials has given us the evidence upon which we have been able to progress in the last half of the twentieth century to introduce a revolution in cancer care. Today, approximately 60% of all cancer patients expect to be cured of their disease. (Prevention and early detection can increase this number to over 80%.) It is very exciting that there are so many new avenues of research showing tremendous potential coming out of the laboratories and waiting to be tested. In Rhode Island an increased number of patients can go onto clinical trials with improved access to these new treatments. In fact, all cancer patients can enter appropriate clinical trials for their specific disease and they will be covered by their insurance and/or Medicare. We can be optimistic that there will be better survival rates in the next decade as a result.

(Part 2 of a two-part series - Click here for Part 1)

For more information and answers to specific questions contact the Rhode Island Cancer Council at Tel@ricancercouncil.org or call us at (401) 728-4800 or toll free 866-879-4100.

IT IS EASIER TO PREVENT CANCER THAN TO TREAT IT.

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