Phase II expansion cohort in colorectal cancer to evaluate the safety and tolerability of RRx-001 blood mix.

Abstract

e16144 Background: In a 34 patient randomized Phase 2 trial in 3rd/4th line colorectal cancer called ROCKET (NCT02096354) of RRx-001 + irinotecan versus regorafenib + irinotecan, RRx-001 + irinotecan demonstrated improved overall survival (OS) (8.6 vs 4.7 months) and progression free survival 2 (PFS2) (7.5 vs. 1.7 months) compared to the regorafenib control arm. The main adverse event attributed to RRx-001 treatment, which involved once weekly peripheral or central infusion, was a painful infusion-related superficial phlebitis in 80% of patients. Following the randomized portion of the ROCKET trial, another 18 colorectal patients were enrolled in an expansion cohort to evaluate the safety and tolerability of an RRx-001 “blood mix”, the objective of which was mitigation of the phlebitic complications of direct RRx-001 infusion. Methods: Therapy consisted of intravenous administration of RRx-001 at 4 mg once weekly via blood mix until progression followed by intravenous infusion of irinotecan at 180 mg/m2 on day 1 in a 21-day cycle. Results: The median OS and PFS2 were 6.3 and 5.2 months, respectively, which was similar to that of RRx-001 administered by direct infusion in the randomized part of the trial. No patients experienced phlebitis. The adverse event profile was otherwise unchanged compared with direct IV infusion of RRx-001. Conclusions: The results of this expansion cohort demonstrate similar activity of RRx-001 given by blood mix followed by irinotecan to RRx-001 given by direct IV infusion followed by irinotecan.RRx-001 alleviated the pain that had been observed in the direct IV infusion and therefore allowed for a shorter infusion time without any apparent compromise in activity (based on OS/PFS2 comparability to earlier results). Finally, since phlebitis in theory may progress to deep venous thrombosis or suppurative thrombophlebitis in hypercoagulable and immunosuppressed cancer patients, blood mix RRx-001 is the preferred method of infusion. Clinical trial information: NCT02096354 .