January 31, 2012
By C.J. Janovy
|Ray Perez, MD|
Shortly after the opening of the KU Clinical Research Center in early January, we spoke to Perez about the kinds of Phase 1 clinical trials KU will be conducting and what makes the new center unique.
What exactly is a Phase I trial?
Phase I trials test drugs in humans for the first time. We're trying to learn the right dose, what the drug does to the patient, and what the patient does to the drug.
To figure out what the drug does to the patient, we note which side effects occur and measure how severe they are. We also target drugs at specific components of cancer biology. We test whether the drug works the same way in patients as it does in the lab. A drug that targets a particular protein might have worked when we treated cancer cells in a dish, but there's no guarantee it'll work the same way in people.
Our other goal is to figure out what the patient does to the drug. If we're going to use a drug intelligently in people, we need to know how often to give it and how the body gets rid of it. Usually that's through the kidneys or liver, and sometimes we have to adjust doses in people whose kidneys or livers aren't working properly. Most Phase I studies measure drug levels over time and how the drug is eliminated. That's how we learn how often to actually give the drug. This also helps us draw conclusions about what the drug does to the patient. If someone experiences a particular side effect, that probably only occurs above a certain drug level.
What is the experience like for patients?
We want to demystify trials and the research process. We have hired a patient navigator so that when a patient or a physician calls the Clinical Research Center, they'll speak to a person who is knowledgeable about trials throughout the cancer center. The patient navigator will know whether we have something for the caller here, on the main campus, or at the Westwood campus.
During their first phone call, the nurse navigator will talk to patients about their history. If the nurse navigator thinks we have something to offer the patient, initial visits will be scheduled with advanced practice nurses and physicians, all focused just on Phase I trials. We'll try to determine three things: where they are in their illness, what they're looking for, and how those align with what studies we have available.
For most patients, determining whether the drug works or not will look familiar. We use the same approach in Phase I as what they've already seen while on standard treatment. For instance, they might have had a CT scan showing what their disease looked like before and after a previous treatment. We do the same thing — compare "before" and "after" scans.
Phase I trials may also include some tests that don't look so familiar. For instance, in order to determine how drugs work in tumors, we may need to obtain small tumor samples or biopsies at various times after drugs are given. We also generally obtain more blood samples than when patients are on conventional treatments, to measure what's happening to drugs in the body.
Aren't Phase I trials for people who have run out of all other options?
Yes and no. Phase I trials are most often offered to patients who have exhausted all conventional options. We don't offer Phase I trials to patients who might reasonably be cured or have their lives prolonged by standard treatments. However, for some cancers, there may not be decent options available for patients who have never been treated. Phase I trials are reasonable there, too.
There does come a point with advanced cancer where it's no longer reasonable to give patients drugs. We don't want to give drugs just to give them something — we want to help. If we can't reasonably do that, we'll steer them toward something that better meets their needs — whether it's a different treatment here or elsewhere, or hospice. We want to clarify the process and their options, and match patients with what they need.
How many cancer clinical trials are going on at the Clinical Research Center?
We currently have eleven Phase I trials underway at The University of Kansas Cancer Center. We're moving most of these to the Clinical Research Center. When we're at full capacity, we expect between 200 and 300 patients per year and will have 25 to 30 trials open at any point in time. We've planned our pharmacy, our infusion space to administer drugs and our support laboratories to handle this volume of patients.
How will you get more trial participants?
As the community becomes more aware of our center, we'll get some self-referrals. We also expect referrals from physicians regionally and nationally. Finally, we expect The University of Kansas Cancer Center's hematology/oncology group to increase its own Phase I activity and to refer patients to trials run by other KU physicians.
As our portfolio grows, we will be adding therapies developed at KU or KU-based startup companies, and also new drugs that come from the pharmaceutical industry.
Also, as a result of the cancer center's merger with the Kansas City Cancer Center, we will have access to the portfolio of trials conducted by US Oncology, one of the largest networks of clinical researchers in the nation.
What drugs are you testing?
We have several interesting drugs in trials right now. Some are old drugs, used for other diseases, which were discovered to have anticancer activity by laboratory scientists on the Lawrence campus. This process, which is called drug repurposing, involves learning to use the drugs we've already got more intelligently. KU scientists are among the worlds' leading experts in repurposing.
For example, we have a trial of Auranofin, an old arthritis drug that our scientists repurposed to treat a rare blood cancer called chronic lymphocytic leukemia. We are also about to open a trial of tigecycline, a close relative of the commonly used antibiotic tetracycline, in patients with acute myeloid leukemia that's relapsed or failed to respond to standard treatment. Several additional trials with drugs repurposed at KU are expected to open within the next few years.
We are also testing drugs from local biotech companies. Crititech, in Lawrence, uses technologies originally developed at KU to package anticancer drugs into extremely small particles (nanoparticles). Nanotax, a nanoparticle formulation of taxol — used to treat ovarian cancer and other malignancies — is currently in a Phase I trial at the Clinical Research Center. A second Crititech drug called nanothecin, a nanoparticle version of irinotecan (used for colon cancer) is expected to enter clinical trials in the near future. Deciphera Pharmaceuticals, also in Lawrence, has developed a drug called DCC-2036 to treat patients with chronic myeloid leukemia or a particular type of acute lymphoblastic leukemia. We have great collaborations with both companies and hope to do a lot more work with them in the future.
Later this spring, we will be opening a National Cancer Institute-funded Phase I trial of conjugated linoleic acid (CLA), a nutritional supplement marketed for weight loss. In the lab, CLA kills cancers that are addicted to certain types of fat. I began this Phase I trial while I was at Dartmouth, and am in the process of transferring the study to KU.
Finally, we have several trials that use drugs from various pharmaceutical companies, targeted against certain proteins known to be important in cancer biology. These trials include drugs that target cancers with abnormalities in a gene called ALK (Crizotinib), the protein MDM2 (RO504337), the proteasome (MLN9708), general gene expression (azacitidine), and a protein called PI3-kinase (BKM120).
What makes this Clinical Research Center so unique?
There are not many places in the country that have free-standing, dedicated Phase I centers. Offhand I know fewer than five. Having a dedicated facility focused on early clinical research matters because this aspect of cancer medicine is very specialized. To properly ask and answer those questions — what the drug does to the patient and what the patient does to the drug — requires a team of experts in things like measuring drug levels in the body. So we have a lab with instruments that will allow us to detect very small quantities of drugs in the body, and people who know how to operate those instruments. It's a tricky thing - these machines aren't so user-friendly that you can push a button and say, "Measure drug X." There's some art to doing the measurements correctly — each assay has to be built from scratch, and properly validated.That's one thing that's unique about our center: We have the capacity to do those measurements right down the hall from where the patient is treated. We don't have to package the sample and send it somewhere else.
Also, we engage the experts who run those measurements in the design of studies well before they open. Then we're more certain to obtain and handle the samples in the right way. It's really important to control each part of the process, from when the sample comes out of the patient until it goes into the machine, to maintain quality.
Finally, there's no place else in the country where voters have passed a sales tax to fund this type of research. Between the public support from the voters of Johnson County and the philanthropy from the Hall Family Foundation, which contributed this building as part of an $18 million gift to the cancer center, I think we've got something really special here.