What is the RADICAL Trial?
The RADICAL trial (ClinicalTrials.gov identifier: NCT04071223) is an ongoing prospective clinical trial enrolling patients with metastatic clear cell renal cell carcinoma (mRCC) and bone metastases to evaluate the combination of cabozantinib plus radium-223 dichloride. 1
Trial Design and Purpose
The RADICAL trial specifically targets patients with mRCC who have developed bone metastases, a population known to have worse prognoses and higher risk of skeletal-related events (SREs). 1
This trial represents an important investigation into whether combining a VEGF tyrosine kinase inhibitor (cabozantinib) with bone-targeted alpha-particle therapy (radium-223) can improve outcomes in this challenging patient population. 1
Clinical Context and Rationale
The trial was designed based on evidence that cabozantinib-containing regimens should be considered for patients with bone metastases, given currently available data showing benefit in this subgroup. 1
Radium-223 is an alpha-emitting radiopharmaceutical that selectively binds to newly formed bone stroma at metastatic sites, inducing double-strand DNA breaks in tumor cells while minimizing damage to adjacent tissues due to the short range of alpha particles. 1, 2
Prior research demonstrated that radium-223 combined with VEGF-targeted therapy (pazopanib or sorafenib) in advanced RCC with bone metastases showed biological activity with significant declines in bone turnover markers and acceptable safety profiles. 3
Why This Trial Matters
Patients with mRCC and bone metastases face elevated risk of SREs including fractures, spinal cord compression, and need for radiation or surgery to bone. 1
The combination approach aims to simultaneously target both the tumor biology (via cabozantinib) and the bone microenvironment (via radium-223), potentially providing dual therapeutic benefit. 1
This trial will help determine optimal treatment strategies for a specific subset of mRCC patients where prospective data is currently lacking. 1
Important Distinction from Prostate Cancer
While radium-223 is FDA-approved and has established survival benefit in metastatic castration-resistant prostate cancer (improving median overall survival from 11.3 to 14.9 months, HR 0.70, P<0.001), its role in RCC remains investigational. 1, 4
The RADICAL trial will provide critical prospective data on whether the benefits seen in prostate cancer translate to the RCC population with bone metastases. 1