The Benefit to Radium-223 Added to Cabozantinib for Patients With Renal Cell Carcinoma With Bone Metastasis, RadiCaL - Rana McKay
March 4, 2023
This rationale for this trial was fueled by a previously conducted small pilot study with Radium 223 with other VEGF TKIs, including pazopanib and sorafenib. The primary endpoint was looking at bone formation and bone resorption biomarkers, and the results showed that Radium 223 could decrease markers across the board in patients receiving combination therapy with a signal of reduction in SSE events.
A Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Advanced Renal Cell Carcinoma With Bone Metastasis (RadiCal) [https://clinicaltrials.gov/ct2/show/NCT04071223 ], The Alliance Trial A031801
Rana R. McKay, MD, Associate Professor of Medicine, Medical Oncologist, Assistant Professor of Medicine, UC San Diego Health
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Alicia Morgans: Hi, I'm so excited to be here with Dr. Rana McKay of the University of California-San Diego. Thank you so much for talking with me.
Rana McKay: Oh, no, it's great to be here. It's a pleasure.
Alicia Morgans: It is always a pleasure to talk with you, and today I really wanted to hear about the RADICAL trial, which is a study looking at metastatic kidney cancer and the use of radium in that population. Can you tell us a little bit about it?
Rana McKay: Oh, yeah, of course. So we know from multiple data series that patients who have bone metastases from RCC do worse. They have worse outcomes, they have worse morbidity and mortality, and they really represent an unmet clinical need in the clinic. And actually the genesis of this trial was seeing these patients in the clinic do poorly, and what can we do to actually improve their outcomes?
So this trial is basically a phase two trial. We're taking patients with RCC with bone metastases. They could have one to any number of bone metastases; any histology, both clear cell and non-clear cell; randomizing them one to one to receive radium with cabozantinib versus cabozantinib alone with a primary endpoint of SSE free survival.
Alicia Morgans: That's so exciting, and really exciting especially that we can use radium to target their metastatic disease more precisely. How did you decide on that cabozantinib control arm, and what do you think about that comparison?
Rana McKay: Very good. So we actually previously conducted a small pilot study with Radium 223 with other VEGF TKIs, including pazopanib and sorafenib, and that pilot study really fueled the rationale for launching this trial. The primary endpoint of that trial was looking at biomarkers of both bone formation and bone resorption, and looking at actually declines in those markers. And we actually demonstrated that we were able to systematically decrease markers across the board in patients receiving combination therapy with a signal with regards to reduction in SSE events.
And that really was the fuel to bring this into a larger study that can more definitively answer the question. Cabozantinib has a long track record for activity in the bone, given it targets c-MET, and it was a very natural partner to combine with radium 223.
Alicia Morgans: Absolutely. And so exciting and such an effective treatment of course for kidney cancer.
Rana McKay: Yeah.
Alicia Morgans: So as you move forward, you're continuing to accrue in this trial. Can you tell us a little bit about what milestones we've met in terms of accrual?
Rana McKay: The study is open through the NCTN, which is the National Clinical Trials Network. Any institution or community site that is a partner with the NCTN can open up the trial at their institution. It's a really simple study. Patients get randomized. Like I said, 1:1 to radium with standard of care with cabozantinib, which will be supported through the context of the trial. There's no biopsies, there's minimal blood collection, and so it's a really a great opportunity to provide this treatment for patients.
Alicia Morgans: Wonderful. Well, we certainly look forward to seeing where this is going to go. Do you have any final words or comments for people who are interested in engaging this trial, perhaps opening it at their site?
Rana McKay: Yeah, I think this is a great unmet need. We just saw at ASTRO the results of the role of stereotactic body radiation for patients with high volume bone metastases actually improving SSEs and overall survival. That study was very provocative, and I think this is one of those studies where really radium is being looked at in a context outside of prostate cancer. There's a very limited number of studies that are actually testing radium and other solid tumor malignancies, so being able to bring forward a radioligand therapy for individuals with RCC is really exciting.
Alicia Morgans: I could not agree more, and I really look forward to continued updates on the radicals trial, and really, ultimately, of course, to the data and hearing the conclusion of this study. So thank you so much for your time and your continued efforts in this area.
Rana McKay: Thank you so much.