Timothy McClure: Thanks for having me.
Leslie Ballas: Oh my gosh, it's so good to see you.
Timothy McClure: I know.
Leslie Ballas: We at UroToday are excited to hear about IRRADIANT. So tell me what it is.
Timothy McClure: So it's a trial that we are doing, randomized controlled trial, that is an expansion of a trial that I started with Himanshu Nagar, who's a radiation oncologist, was at Cornell but moved to Sloan Kettering. And one day we were chatting after work, and we're discussing focal therapy and some of the limitations with it, which is really recurrence. And the concept of focal therapy is, what's a way to de-escalate standard of care, surgery, radiation therapy to really minimize the toxicity that's associated with those treatments? And clearly there's a lot of interest in focal therapy to minimize those, but it comes at a cost, and that's oncologic efficacy.
And so in discussion, we thought, "Well, why don't we just combine a focal approach with a lower dose whole-gland radiation therapy?" And so we came up with this idea of first treating a patient with focal therapy, specifically irreversible electroporation, and then follow that with radiation therapy. So it started out as a phase-one trial, then moved to phase-two. And we had good outcomes, and so are now moving to a randomized controlled trial comparing radiation with a radiation boost to the prostate compared to, basically, RTIRE, which is focal IRE followed by radiation therapy.
Leslie Ballas: Explain to me as a radiation oncologist, how is IRE different from cryotherapy or HIFU?
Timothy McClure: So it's different in both HIFU and cryo use either freezing or heat to kill tissue where IRE uses basically electricity to cause electroporation, which performs whole in the cell membrane and then that cause apoptosis. So it's a non-thermal ablative approach.
And the reason why we chose IRE over cryo or HIFU, for example, is that it is needle-based and you can treat it throughout the prostate. So you can treat posteriorly, which you can treat with HIFU. You can treat anteriorly, which you could treat with cryo. So it basically allows you kind of treat throughout the prostate. We also thought it had the lowest side-effect profile compared to cryo or HIFU. So that's why we chose IRE.
Leslie Ballas: And what is the typical side-effect profile with IRE?
Timothy McClure: Well, what you expect with all treatments: erectile dysfunction, risk for incontinence. But with incontinence, the risk is very low, less than 1%, and there's a better outcome with regards to sexual function after IRE, particularly if men are potent beforehand.
Leslie Ballas: And I assume from the phase-one, phase-two trials that there was no synergistic side effects of radiation and IRE?
Timothy McClure: There were no synergistic side effects. There seems to be some... Well, we don't know, and that's what this trial is going to help us figure out. But we were surprised at how well the PSA kinetics and the biopsy results were. So for the phase-two trial, it was a 42-patient trial. We biopsied 40 of those 42 patients, and all of them had negative biopsies, no cancer in them. And then the PSA kinetics matched what you'd see with radiation at like two years. So by three to six months, the PSA dropped by about 90%. We're not sure why it's... I'm sure it's just the combined approach from it, but that's why we're excited to move forward with the trial.
Leslie Ballas: Yeah, that's wonderful. How many patients are you looking to accrue?
Timothy McClure: So it's 224. It's a non-inferiority, and there'll be, essentially, patients with intermediate-risk prostate cancer who do not need ADT, and it's a two-year trial. So the primary endpoint is positive rate at biopsy at two years.
Leslie Ballas: What is the null hypothesis? What is the sort of biopsy rate at which you think this would not be beneficial?
Timothy McClure: Yeah. We think there should be a biopsy rate of about 10%. So that's what we're-
Leslie Ballas: 10% positive?
Timothy McClure: Yeah, positive rate from that. So that's what we're aiming for or establishing, I guess.
Leslie Ballas: Where are you at in terms of your accrual?
Timothy McClure: So right now we just opened at Sloan, and we're at three other academic sites. So Cornell is one that's about to activate. Then we're looking at Mayo, UT Southwestern, and Moffitt, so for academic centers trying to get this going on. So we're excited about it.
Leslie Ballas: That's awesome. And just as a radiation oncologist, I must ask, what is the lower dose to the whole-gland that you're using?
Timothy McClure: The dose is we're doing basically focal IRE, and then six weeks later we do five fractions. And it's 36 gray divided by five, so whatever that is.
Leslie Ballas: Yeah. Okay. Well, this is really exciting. Congratulations.
Timothy McClure: Thanks.
Leslie Ballas: I can't wait to see what you guys find. Will you promise that in AUA 2028-
Timothy McClure: Yes.
Leslie Ballas: ... 2029 that you'll-
Timothy McClure: Whenever it gets done, we'll be back with the results. I'm looking forward to it.
Leslie Ballas: Wonderful. Thanks again, Dr. McClure.
Timothy McClure: You're welcome. Thanks for the interview.