Abstract CT154: Multicenter open-label, phase II trial, to evaluate the efficacy and safety of liposomal irinotecan (nal-IRI) for progressing brain metastases in patients with HER2-negative breast cancer (The Phenomenal Study)
Authors: Cortés Javier , Paez David , García José Manuel Pérez , Tormo Salvador Blanch , Parraga Kepa Amillano , Borrego Manuel Ruiz , Torres Antonio Antón , Fernández María , Conejo Emilio Alba , Palmer Miguel Ángel Seguí , Ribugent Joan Dorca , López López Rafael , Vila Mireia Margelí , Aguirre Elena , Llombart Antonio 
Published: August 2018

Abstract
Background: HER2-negative metastatic breast cancer (MBC) patients with central nervous system (CNS) involvement previously treated with a local therapy had very few possibilities of disease response with conventional systemic treatments. Liposomal irinotecan (nal-IRI) is a novel formulation of irinotecan. It has shown promising activity in patients with CNS involvement. The aim of this trial is to evaluate the efficacy of nal-IRI as single agent in HER2-negative MBC patients with CNS progression following local treatment with surgery, stereotactic radiosurgery or whole-brain radiotherapy.
Trial design: This is an open label, non-randomized, multicenter two-stage phase IIA clinical trial. Patients will receive intravenous nal-IRI in a fixed dose of 60 mg/m2 expressed as irinotecan hydrochloride trihydrate salt on day 1 of a 14-day cycle until progression or unacceptable toxicity. The principal selection criteria are: (1) HER2-negative inoperable MBC with CNS involvement; (2) prior local treatment with surgery, stereotactic radiosurgery or whole-brain radiotherapy; (3) prior treatment with taxanes; (4) at least one measurable brain lesion according to RECIST v1.1 criteria. The primary objective is to evaluate the efficacy of naI-IRI monotherapy. Primary endpoint is the CNS overall response rate (ORR), defined as the percentage of patients who experienced complete (CR) and partial response (PR) (as best response). It will be assessed in accordance with the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. The trial uses a Simon's minimax two-stage design. We hypothesized that excluding a CNS ORR ≤5% while targeting an improvement of the CNS ORR to ≥15% would be an optimal approach for evaluating the study strategy. At least 2 responders among 23 patients will be necessary to proceed to the second stage. At the study end, ≥6 responders out of 56 evaluable subjects are required to justify this strategy in further clinical trials. Considering a drop-out rate of 10%, a sample size of 63 patients will be needed to attain 80% power at nominal level of one-sided alpha of 0.05. The secondary objectives include safety-related outcomes and efficacy measures: CNS clinical benefit rate (CR, PR and stable disease [SD] ≥12 weeks), ORR according to a CNS volumetric parameter (CR, PR and &gt;65% reduction of CNS lesion), clinical benefit rate (CR, PR and SD ≥24 weeks), progression-free survival and overall survival. Trial registration: NCT03328884. Date of registration: November 1st, 2017. First patient included: July, 05th 2017.
Citation Format: Javier Cortés, David Paez, José Manuel Pérez García, Salvador Blanch Tormo, Kepa Amillano Parraga, Manuel Ruiz Borrego, Antonio Antón Torres, María Fernández, Emilio Alba Conejo, Miguel Ángel Seguí Palmer, Joan Dorca Ribugent, Rafael López López, Mireia Margelí Vila, Elena Aguirre, Antonio Llombart. Multicenter open-label, phase II trial, to evaluate the efficacy and safety of liposomal irinotecan (nal-IRI) for progressing brain metastases in patients with HER2-negative breast cancer (The Phenomenal Study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT154.