Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial.

Background: The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment.

Methods: Treatment-naïve patients received pazopanib according to standard of care. Stereotactic body radiotherapy (SBRT) was delivered concurrently to the largest metastatic lesion at day 8, 10 and 12. SBRT doses were escalated in 3 dose levels (24 Gy/3, 30 Gy/3 and 36 Gy/3). Dose level was assigned using Time-to-Event Continual Reassessment Method with the target dose-limiting toxicity rate set to 0.25.

Results: Thirteen patients were included. One patient experienced dose limiting toxicity (DLT) at dose level 3 (grade 4 hypoglycemia). Maximum tolerated dose was not reached with a recommended dose of 36 Gy/3 having a probability of DLT of 11%. One-year local control was 83% (95% confidence interval 61-100) and 1-year progression-free survival was 28% (95% confidence interval 1-55).

Conclusions: SBRT in combination with pazopanib is well tolerated with good local control and response rates outside the radiation field.

Trial Registration: This trial was retrospectively registered on clinicaltrials.gov( NCT02334709 ) on January 6th, 2015.