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ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO. The worlds' leading professional organization for doctors that care for people with cancer.

In todays' podcast, we'll discuss phase one clinical trials. The purpose of a phase one clinical trial is to learn how safe a new drug or therapy is for people, find the best dose and schedule, and study how it might help treat cancer. This podcast will be led by Dr. Jeffrey Weber, who is Director of the Moffit Cancer Centers Donald A. Adam Comprehensive Melanoma Research Center and Professor and Associate Chair of the Department of Oncologic Sciences at the University of South Florida. Dr. Weber is also a member of the ASCO Cancer Research Committee.

ASCO would like to thank Dr. Weber for discussing this topic.

Dr. Weber: This is Jeffrey Weber, and I am a medical oncologist and a clinical researcher at the Moffit Cancer Center in Tampa, Florida. I'm going to discuss a new policy statement from ASCO, which is the American Society for Clinical Oncology, our professional organization, about phase I clinical trials and what they mean for patients. Clinical trials are the means by which we find out whether new drugs or treatments for cancer are safe, and how well they work in patients. Clinical trials involve testing of groups of patients with similar types of cancer or similar stages of advanced cancer.

These clinical trials are described as phase I, phase II, and phase III, which refers to the reason why and the manner in which they are conducted. It's the first group that we are most interested in today, the so-called phase I trial. These trials are most often performed using increasing doses of a drug or treatment, usually in patients with cancer that has spread or metastasized and cannot be cured with surgery or radiation. Most often, those patients have had standard therapy or had already been on another trial which failed to shrink their cancer. The first time that a new cancer drug or therapy is tested in people is usually a phase I clinical trial.

The U.S. Food and Drug Administration, known as the FDA, requires that all new cancer treatments undergo testing to find out if the drug is safe and the best dose to use. Cancer investigators are required to find the best schedule of doses, how long the treatment should be, and whether the drug or treatment can shrink specific types of cancer. The other purpose of performing a phase I trial is to find out what the proper dose is to move onto the next step in development of a new cancer treatment, what we call the phase two study.

The phase II study usually includes a large number of patients with the same type of cancer, all of which are treated the same way, to find out how well the drug or treatment shrinks the cancer. Then if things look encouraging, a phase III head-to-head comparison of the new drug or treatment with standard therapy is done, to pick the winner in an even larger number of patients. If the new treatment is better than the standard, then it will be likely to become the new standard of care for that cancer.

Today we're concerned with the first type of study which is the phase I trial. In the past, there has been much misunderstanding about the purpose of doing a phase one trial. Many patients thought that there was no hope of gaining benefits for themselves from participation in a phase one study and that the purpose of the study did not include shrinking cancer and potentially helping patients. That has never been the case, and it is certainly true today that the chance of getting benefits from the phase one trial has never been higher. Oncologists seek to use doses of drugs or new treatments that are as close to the effective dose in their phase one trial, and then to start increasing the doses from that point. Subsequent phase I studies, called phase Ib studies, may also test new schedules of existing treatments or combinations of new treatments even radiation. These trials may also measure the side effects and effectiveness of a new treatment in types of patients that had been excluded in prior phase one studies.

In addition, researchers are increasingly conducting phase one studies that become expanded to include hundreds of patients. And that also include a clear measure of how well the drug or treatment shrinks tumors in large numbers of patients. In the past few years, we've even had trials that have included as many as 400 patients, that started out as a phase I study but essentially became converted to much larger studies that tested the effectiveness of the drugs. In the era of new treatments and drugs that are called molecularity targeted, factors other than how many side effects there are may influence the oncologists' ability to find out what dose of the drug to take forward to test in future studies.

New trial designs also allow oncologic researchers to more quickly escalate the dosage of the agent that patients are receiving to levels that are more likely in the ability to shrink tumors. If a drug's target is very well defined, these new types of phase one studies also permit oncologists to only choose the patients that are most likely to have disease that is driven by the target being hit by the new drug or agent, which increases the likelihood of benefit for the patient. Patients that participate in phase one trials have been found to have an increased quality of life, increased psychological well-being, and significant benefit from a defined plan of treatment.

In addition, patients participating in clinical trials generally report satisfaction with their medical care, and superior management of pain and other symptoms. Many patients feel empowered by taking control of their cancer care when they're part of a clinical trial. Of course, many patients are motivated to help other people with cancer. Over time it has been shown that the rate of tumor shrinkage in phase one trials is considerable, often as much as one in ten. Therefore, the fear that patients in phase I trials are guinea pigs or hopeless cases without chance of benefit, is simply untrue.

All cancer patients should inquire of their oncologists if they should be considered for a clinical trial, and if not, why not? We've come a long way in the last 20 years in cancer research with more people being cured and enjoying prolong survival after a diagnosis of cancer. Of course, there's still a long way to go, and there will be no further progress unless there is large scale participation by cancer patients in clinical trials.

Increasingly, the treatments tested in our phase I clinical trials help shrink tumors or stabilize the cancer for many patients, because today appropriate drugs can now be matched to the suitable patients. New study designs allow for more efficient testing of new drugs and therapies. If a patient has had their tumors grow in spite of the standard approved treatments, then they should ask their oncologist if a phase one trial is available to them in their own office. Or if not, where the nearest medical center is that might offer it. If patients do participate in phase one trials, they should be aware that many states require that insurers cover the routine and ordinary costs of being in that trial. Those are the costs, by the way, that would have occurred had they received treatment other than the phase one trial.

There are a number of reasons why ASCO has published this new policy statement on phase I trials. An important reason is to improve insurance payer’s coverage of routine patient costs in phase I trials so that more patients may have access to the potential benefit of those trials. We also wish to improve patients and oncologists understanding of the goals of phase one trials, which particularly include the ability to provide benefit to patients. We wish to increase the number of patients who enroll in phase one trials so that progress in the field of cancer research and treatment may advance. Specifically, it's important to increase support for phase one trials in children with cancers, since many drug companies have been reluctant to test new drugs or agents in children soon after they're testing in adults. That policy has slowed down the ability to treat children with new drugs that might benefit them.

In closing, there are a number of questions that patients should ask their doctor or research team. They include questions like, what clinical trials are open to me as a patient? Where are they located, and how do I find out more about them? One should know what is the purpose of the clinical trial. One should also ask, while being involved in a trial, what are the possible risks of the involvement. What are the potential benefits of being in the clinical trial? One should also ask why the physician is recommending this specific clincal trial. One should ask, what other treatment options are available? And important question is whether any clinical trial includes the use of a placebo which is in inactive treatment. It's important to know who'll be coordinating a patient’s overall care if they enroll at a clinical trial. Critical questions also include what costs are associated with the clinical trial. Patients should ask assistance to find out what costs are covered by insurance and what costs patients might be responsible for. Finally, if a patient is worried about the costs related to cancer care, they should be able to find out who can help them. Overall, we're now in a new era, and more than ever before clinical trials will help lead to major advances in cancer care. Thank you very much for listening.

ASCO: Thank you Dr. Weber. More information about clinical trials can be found at www.cancer.net/clinicaltrials.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding break-through research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high quality cancer care. Thank you for listening to this Cancer.Net podcast.

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