1. DiGiulio, Sarah

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The American Society of Clinical Oncology's first clinical trial recently opened for enrollment of patients. The trial-the Targeted Agent and Profiling Utilization Registry (TAPUR) study first announced at the 2015 ASCO Annual Meeting (OT 8/25/15 issue)-was designed as a multi-arm, Phase II, basket study to evaluate molecularly-targeted cancer drugs and collect data on clinical outcomes of patients on these drugs used outside of indications already approved by the U.S. Food and Drug Administration.

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"TAPUR is a mechanism to learn about the real-world prescribing of targeted drugs used off-label for the treatment of patients with advanced cancer whose tumors have a genetic profile test performed and reveal some type of genetic abnormality that might be targeted by a targeted anticancer agent," explained Richard L. Schilsky, MD, FACP, ASCO's Chief Medical Officer who has helped lead the charge on launching TAPUR.


The trial (NCT 02693535) has launched at 30 clinical sites located in Michigan, North Carolina, South Carolina, and Idaho-with plans to expand further by the end of the year.


"Part of ASCO's mission is to learn from observing the practice of medicine. TAPUR is organized along this philosophy, focusing specifically on the precision medicine space," Schilsky said. "There are two problems-patients often have a test result that indicates a particular drug might be helpful to them, but then they have big problems getting access to the drug because if it's a commercial drug being used off label, it's often not covered by insurance-and drugs are very expensive. And even if the patients are able to get access to the drugs, the other problem is nobody's been able to learn anything from the experience of those patients getting those drugs.


"TAPUR provides us another mechanism to learn how precision medicine is being deployed in practice and whether it's working or not," Schilsky said. "We felt that there was a need and an opportunity now."


So how does it work? In a phone interview, Schilsky explained who should enroll and how clinicians can help get their patients on the trial.


1 Who should enroll in the trial? Which patients are most likely to benefit?

"The trial eligibility includes all patients with advanced solid tumors, non-Hodgkin lymphoma, or multiple myeloma who have exhausted all standard treatment options or for whom no standard treatment options exist. Those are the patients we're looking for.


"The trial will launch in only a limited number of clinical sites initially. The reason for that is because we need to be sure that all of the trial logistics are performing as they should be-that the data capture measures are all in place, as well as the safety parameters. Our hope is that everything will go smoothly and probably by midyear we'll begin expanding access to the study across the country.


"We have a long list of clinical sites around the country who have already expressed interest in joining the study, and hopefully by the second half of the year, we'll be getting it out there nationally."


2 Once the trial expands, how does a cancer center join the trial? And how do physicians enroll their patients?

"All of the participating sites have signed a formal study participation agreement with ASCO to be a study participant site. And they've all received the protocol, which is approved by a central IRB, but the site has the discretion to also submit [the protocol] to their local IRB.


"Then it looks like pretty much any clinical study. There is a two-step eligibility process-patients first need to meet the general eligibility criteria for the study. And then once the specific drug is selected that they'll receive, there is drug-specific criteria the patient needs to meet.


"The key to enrolling in TAPUR is the treating physician deciding to do a tumor genomic test. In the spirit of having this be a real-world trial that tries to understand what is going on in practice, whether to order a test, which test to order, and which patient specimens to do the test on, is all left to the discretion of the treating physician.


"Once [the physician] has the genomic tests results in hand and a genetic abnormality is identified that matches with one of the drugs available in this study, they can go ahead and register the patient and propose the drug of genomic match they want to use. There's an automated rule in the IT platform of the study that will approve the match or not depending on whether the match comports with the rules in the protocol.


"If the match is approved then the patient can go on and be formally enrolled and receive the treatment. If the match is not approved, then the physician has the option to consult with the TAPUR molecular tumor board, in which case the virtual tumor board would convene by webinar. They'll review the case and identify what they consider to be a reasonable treatment option for the patient. If they agree with the physician's proposal to use the TAPUR drugs, the patient then can continue in the protocol and receive the treatment.


"The board might recommend a different drug that's in the TAPUR protocol; or if they recommend a drug that's not in TAPUR protocol and the doctor wants to use that option then the patient is no longer followed in the protocol.


"For patients who do enroll, once they start treatment, there's an initial major evaluation that occurs after 16 weeks on the study. The patients can continue on the treatments as long as they have either stable disease or responding disease. Whenever patients have progression they come off that particular treatment."


3 When do you expect to report results from the trial?

"It depends how quickly the study enrolls. And there's not a specific number of patients that need to enroll before we can report results. We're going to be reporting results in different groups of patients at different times-by analyzing by cancer diagnosis, the genomic abnormality, and the drug that is used.


"For example if the group was patients with bladder cancer that had a BRAF mutation and got treated with a BRAF inhibitor-that would be a group. And there could be hundreds or thousands of those groups because there are so many genetic abnormalities in tumors.


"In each of those groups we'll initially enroll 10 patients. If there are no responses or only one response, we'll stop enrolling in that particular group. If we see at least two responses, the plan is to enroll 18 additional patients for a total of 28. And for the final analysis, if we see at least seven responses, we'll say that drug has a signal of activity and should be followed up with additional studies or additional data from other sources to confirm that drug has activity in that particular tumor type.


"Whenever we reach those milestones, we'll report out the data-if we close a cohort because of no sign of activity, if we expand a cohort out to 28, etc. I think it's unlikely that we'll have data to report until sometime in 2017."