Importance of Phase III Clinical Trials

Position Papers and Reports

Importance of Phase III Clinical Trials
An Interview with Jordan Berlin, MD

Clinical trials are research studies that investigate new treatments or new combinations of treatments. They play an important role in the development of new treatment options for pancreatic cancer. Pancreatic cancer clinical trials are necessary to determine whether new treatments are beneficial to people living with the disease. The Pancreatic Cancer Action Network recommends that all patients consider clinical trials when exploring treatment options.

Jordan Berlin, MD, serves as Associate Professor and Clinical Director of GI Oncology and Phase I Program at the Vanderbilt University Medical Center in Nashville, Tennessee. He also serves as the chair of the organization’s Medical Advisory Board. Recently, he shared his thoughts on the importance of clinical trial participation.

Q: Why are clinical trials important in pancreatic cancer?
A: Clinical trials are more important in pancreatic cancer than in any other cancer because we have not yet particularly succeeded in improving patient survival. Without clinical trials, we will not develop new drugs and new treatments that will hopefully increase survival and the cure rate of this disease.

Q: What are the potential benefits and risks of clinical trials?
A: The benefits and risks come from the same issue: the outcome of the trial is unknown. Patients could possibly benefit more from the new (experimental) treatment than the current standard treatment. There is also the risk that the new treatment may be less effective than the standard treatment. However, most of the time, when a clinical trial is not successful, it does not mean that the new treatment is worse than the standard treatment. It simply means that the new treatment is not better than the standard treatment. Another benefit of participating in a clinical trial is receiving top-notch supportive care.

Q: Who should consider participating in a clinical trial?
A: Most pancreatic cancer researchers believe that all patients who have the option and are eligible should consider a clinical trial. Because pancreatic cancer treatments are not as effective as we would like, many consider clinical trials as a standard of care option for patients with pancreatic cancer. Patients should consider clinical trials each step of the way, if possible. Patients should investigate their clinical trial options from the very beginning, because it starts them on a path of learning about clinical trials and the potential for participating in multiple clinical trials.

Q: What are the different phases of trials?
A: Clinical trials have three main phases: Phase I, II and III. Phase I is the first chance in the research process either to combine new drugs together or to give a patient a brand new drug. The goal of the trial is to learn about the side effects of the drug and how the body uses it, and to determine the highest dose that can be given safely. The dose established in a Phase I trial is used as the proper dose in a Phase II trial.

A Phase II trial enrolls a group of patients with the same disease. This phase is the first disease-specific trial using the new treatment. The goal is to find out how effective the new drug is compared to what we have seen in the past from other trials or with other drugs. Some Phase II trials are randomized, which means that patients are randomly assigned by a computer to one treatment or another. If a new drug or combination of drugs show promise in a Phase II trial, we compare them to the standard of care in a Phase III trial.

The goal in a Phase III trial is to find out if the new drug or combination of drugs is better than or equivalent to the standard of care, and if the benefits of the new treatment will make us change the way we treat patients. All Phase III trials are randomized.

Q: What is the importance or significance of Phase III trials?
A: Phase III trials are the best way to find a new standard for treatment. Once a Phase III study is completed, the groups of patients can be directly compared to one another to evaluate outcomes. (In other words, researchers can see if one group did better than the other group.) If the patients on the new treatment did better, a new standard of care may be established.

Therefore, this type of trial may result in drugs gaining approval by the FDA and changing the way doctors treat patients. Promising treatments may emerge in other phases, but those trials are not definitive enough to change standards of care or the way we treat patients.

Q: What are the benefits for patients who participate in Phase III trials?
A: Hope. Hope that something in the new trial may give the patient a better treatment option. And, if not them, that the treatment or the results of that trial will help other patients in the future.

Another benefit is the chance to participate in new research and potentially receive a new drug. Not every patient will get the new drug but every patient will at least get the standard of care. However, it is unlikely that patients will be able to access that new drug in any other way except participation in the trial.

By the time a drug gets to a Phase III trial, it has the most evidence of both safety and efficacy.

Q: Why should patients consider enrolling in a Phase III trial?
A: The reason to choose a Phase III trial, or any trial, should be based on what the patient has learned about the trial. The benefit of participating in a Phase III trial as compared to a Phase II trial would be that more is known about the treatment. So, the safety is a little more assured, and a stronger potential exists that the new treatment will be better than the standard treatment. However, some patients prefer not to be randomly assigned and they choose a Phase II trial. The bottom line is that all trials are needed; we need patients to enroll in every phase in order to make progress.

The specific criteria for each trial need to be reviewed by the physician who is recommending the trial so a patient knows what may be an option.

To learn more about clinical trials, or to receive a list of clinical trials in your area, contact a PALS Associate toll-free at 877-272-6226 or email pals@pancan.org.