
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.092
vdae090.092
Final Category: Ongoing Clinical Trials
AcademicSubjects/MED00300
AcademicSubjects/MED00310
OCTS-07 TRIAL IN PROGRESS: PHASE II STUDY OF RADIATION THERAPY FOLLOWED BY INTRATHECAL TRASTUZUMAB/PERTUZUMAB IN THE MANAGEMENT OF HER2+ BREAST LEPTOMENINGEAL DISEASE
Ahmed Kamran Moffitt Cancer Center, Tampa/FL, USA

Kumthekar Priya Northwestern University, Chicago/IL, USA

Kim Youngchul Moffitt Cancer Center, Tampa/FL, USA

DeJesus Michelle Moffitt Cancer Center, Tampa/FL, USA

Pina Yolanda Moffitt Cancer Center, Tampa/FL, USA

Oliver Daniel Moffitt Cancer Center, Tampa/FL, USA

Evernden Brittany Moffitt Cancer Center, Tampa/FL, USA

Arrington John Moffitt Cancer Center, Tampa/FL, USA

Vogelbaum Michael Moffitt Cancer Center, Tampa/FL, USA

Rosa Marilin Moffitt Cancer Center, Tampa/FL, USA

Soliman Hatem Moffitt Cancer Center, Tampa/FL, USA

Yu Michael Moffitt Cancer Center, Tampa/FL, USA

Han Hyo Moffitt Cancer Center, Tampa/FL, USA

Forsyth Peter Moffitt Cancer Center, Tampa/FL, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i28i28
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

BACKGROUND

HER2+ leptomeningeal disease (LMD) has a poor prognosis with a high unmet clinical need. A previous phase I/II study revealed intrathecal (IT) trastuzumab to be well tolerated with improved overall survival (OS) compared to historical controls in HER2+ breast LMD. Radiotherapy can improve the flow of IT therapy through the cerebrospinal fluid (CSF) and provide symptomatic relief. The monoclonal antibody pertuzumab is used in conjunction with trastuzumab in the systemic management of HER2+ breast cancer. The phase I portion of the current study used a modified toxicity probability interval-2 (mTPI-2) design to determine 80 mg IT pertuzumab as the recommended phase II dose with a fixed dose of 80 mg IT trastuzumab.

METHODS

The study is designed as a prospective, single-arm, nonrandomized, open-label, phase II trial of radiation therapy followed by IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. HER2+ LMD patients identified by magnetic resonance imaging (MRI) and/or CSF cytology, ≥18, with a life expectancy > 8 weeks are eligible. Treatment is initiated with radiotherapy, whole brain radiotherapy and/or focal brain/spine radiation followed by IT trastuzumab/pertuzumab. The primary objective of the phase II portion is to evaluate OS following IT trastuzumab/pertuzumab. Secondary objectives involve evaluating the response rate (leptomeningeal and parenchymal), and progression free survival (leptomeningeal and parenchymal). A single-arm two-stage trial is designed using the Restricted-Kwak-and-Jung’s Method. The primary endpoint is one-year OS. An interim analysis will be performed after 20 patients are enrolled with plans to enroll an additional 10 patients if criteria are met. This study is open with 14 patients enrolled at the time of submission. Clinical trial information: NCT04588545.
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