Clinial trials are carefully controlled research studies in which patients may participate. These studies may test whether a new treatment is safe and how well it works in patients, or look at new ways to diagnose or prevent a disease. Clinical trials may also focus on refinements to existing standard therapies. Most of the advances in cancer therapy have resulted from the participation of patients in clinical trials.

Physicians may ask patients if they would like to participate in a clinical trial, and there are advantages for patients who choose to do so. First, they will be assured of receiving state-of-the-art cancer care according to a very specific plan of treatment. Second, physicians who participate in clinical trials stay up-to-date with the newest cancer treatments, keep careful track of all of the results of treatment--both good and bad--and compare their results with those of other colleagues to further refine treatment strategies. There are many decisions to make after a cancer diagnosis, and one of them may be whether or not to participate in a clinical trial. 

The Purpose of Clinical Trials

Clinical trials are conducted to get a closer look at promising new treatments or procedures in patients. A clinical trial is only done when there is good reason to believe that the treatment, test, or procedure being studied may be better than the one in use now. Treatments tested in clinical trials are often found to have real benefits and may go on to become tomorrow’s standard treatment.

NCCN is strongly committed to clinical trials and believes that the best management for any cancer patient is in a clinical trial.

Clinical trials can focus on many things:

• New uses for drugs that are already approved by the U.S. Food and Drug Administration (FDA); for example, drugs used in one type of cancer may be tested in another type of cancer or different drugs may be combined

• Different ways of administering chemotherapy, such as using oral drugs instead of IVs

• New drugs that have not yet been approved by the FDA, where research is being done to determine the best dosage to balance side effects with effectiveness

• Different types of radiation therapy designed either to decrease the side effects of radiation; allow higher, more effective doses of radiation; or both

• “Alternative medicines” such as herbs and vitamins

• New diagnostic tests, such as genetic tests, to determine which patients are the best candidates for certain therapies or whether a particular chemotherapy regimen is likely to be effective

• Medicines or procedures to relieve symptoms or improve comfort The following sections review different kinds of clinical trials.

Phases of Clinical Trials

There are four phases of clinical trials, numbered I, II, III, and IV, which are described as follows using the example of a drug therapy.

Phase I Clinical Trials

The purpose of a phase I study is to find the safest way to give new treatment to patients. The cancer care team closely watches patients for any harmful side effects.

For phase I studies, the drug has already been tested in lab and animal studies but needs to be tested in humans to understand the optimal dose balanced against the level of side effects. Since phase I trials represent the earliest type of trial in humans, most patients in these trials have not been successfully treated with standard therapies. Doctors start by giving very low doses of the new drug to the first patients and increasing the doses for later groups of patients until side effects appear or the desired effect is seen. These physicians certainly hope to help patients by finding better treatments, but the main purpose of a phase I trial is to test the safety of a new drug. If a drug is found to be reasonably safe in phase I studies, it can be tested in phase II clinical trials. 

Phase II Clinical Trials

These studies are designed to see if the drug works for a specific type of cancer, such as multiple myeloma. Phase II trials frequently involve new combinations of existing drugs. Patients are closely watched for an effect on the cancer, often through the use of different imaging tests (e.g., x-rays, CT scans, or MRI) that show whether the tumor is shrinking. The cancer care team also looks for side effects.

Phase II trials are conducted in larger groups of patients when standard treatments aren’t working. If a drug or combination of drugs is found to be effective in phase II studies, it can be tested in phase III clinical trials.

Phase III Clinical Trials

Phase III studies involve large numbers of patients. Often these studies are “randomized,” meaning that patients are randomly assigned to one of two (or more) treatment groups. One group (called the control group) gets the standard, most accepted treatment, while the other group(s) gets the new treatment(s) being studied. Neither patients nor physicians can pick which group they are assigned to, which may make some patients uneasy, but the doctor will explain the exact rationale for the clinical trial and the risks and benefits of either group assignment. All patients in phase III studies are closely monitored. The studies will be stopped early if the side effects of the new treatment are too severe or if one group has much better results than the others.

Phase III clinical trials are usually needed before the FDA will approve a new drug for use by the general public.

Phase IV Clinical Trials

Once a new drug has been approved by the FDA and is available for all patients, it may be studied in phase IV trials in very large numbers of patients with different types of cancer. This way more can be learned about short-term and long-term side effects and safety. For example, some rare side effects may only become apparent in phase IV studies. Doctors can also learn more about how well the drug works and whether it might be helpful when used in other ways, such as in combination with other treatments.

Deciding to Enter a Clinical Trial

Patients who are interested in taking part in a clinical trial should begin by asking their doctor if the clinic or hospital participates in clinical trials. Next, in order to take part in a clinical trial, patients need to meet certain requirements; in other words, all study participants must be similar in terms of their cancer and general health. This consistency ensures a greater degree of accuracy when the results of a clinical trial are interpreted, meaning the physician can be certain that any improvement in outcome is the result of the treatment and not different patient or cancer characteristics. Finally, the decision about whether or not to participate in a clinical trial is always left up to the patient.

Anyone participating in a clinical trial is required to sign a document called an “informed consent.” The informed consent describes the study in detail and outlines the risks and benefits involved. Doctors and the cancer care team will also explain all the details of the clinical trial, as well as why it may be right for the individual patient. By signing the informed consent, patients indicate that they understand the risks and benefits and agree to participate in the clinical trial. However, signing the informed consent does not mean that patients have to stay committed to the clinical trial; they can withdraw from it whenever they want to for any reason. It is also important to understand that participating in a clinical trial does not keep patients from getting any other medical care they may need.

Questions that patients may wish to ask about clinical trials include:

• Is there a clinical trial that I could take part in?

• What is the purpose of the study?

• What kinds of tests and treatments does the study involve?

• What does this treatment do? Has it been used before?

• Will I know which treatment I receive?

• What is likely to happen in my case with, or without, this new treatment?

• What are my other choices and their pros and cons?

• How could the study treatment affect my daily life?

• What side effects can I expect from the study treatment? Can the side effects be controlled?

• Will I have to stay in the hospital? If so, how often and for how long?

• Will the study cost me anything? Will any of the treatment be free?

• If I am harmed as a result of the research, what treatment am I entitled to?

• What type of long-term follow-up care is part of the study?

• Has the treatment been used for other types of cancers?

Finding Out More About Clinical Trials

People can get a list of current clinical trials by calling the National Cancer Institute’s Cancer Information Service toll-free at 1.800.4.CANCER (1.800.422.6237) or by visiting the NCI clinical trials website at www.cancer.gov/clinicaltrials. Based on information the user provides about the patient’s cancer, this service can put together a list of clinical trials that match the patient’s medical needs. The service can also identify a nearby treatment center based on the patient’s location and willingness to travel for care.

This is an extract from the NCCN Guidelines for Patients^®. NCCN Guidelines for Patients^® on specific cancers are available to view or print out.