MMAP-05 PHASE I STUDY OF CONCURRENT PAXALISIB AND RADIATION THERAPY IN PATIENTS WITH SOLID TUMOR BRAIN METASTASES OR LEPTOMENINGEAL METASTASES HARBORING PI3K PATHWAY MUTATIONS: RESULTS FROM THE DOSE-ESCALATION COHORT

ABSTRACT: Abstract

INTRODUCTION

Radiation therapy (RT) is an effective treatment for patients with central nervous system metastases, but disease control is poor in patients with tumors that harbor PI3K pathway alterations. We hypothesized that combining RT with paxalisib, a CNS-penetrant small molecule PI3K/mTOR inhibitor, could abrogate this effect via downregulation of prosurvival pathways.

METHODS

This is a single institution, open-label, phase I trial of concurrent paxalisib and RT (NCT04192981) for patients with brain metastases, leptomeningeal metastases, or both with PI3K pathway mutations. Part A comprised a standard 3 + 3 dose escalation of paxalisib at 45mg, 60mg, or 75mg daily for two weeks with concomitant RT. The primary objective was to establish the maximum tolerate

SUBMITTER:  

PROVIDER: S-EPMC9354144 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature