A protocol of a single arm, prospective, open-label, multicenter, phase II study of ramucirumab and erlotinib in treatment-naïve non-small cell lung cancer patients with EGFR mutation and brain metastases (SPIRAL-BRAIN study)

Ryo Sawada; Naoya Nishioka; Young Hak Kim; Fumiaki Kiyomi; Junji Uchino; Koichi Takayama

doi:10.21037/tlcr-23-109

A protocol of a single arm, prospective, open-label, multicenter, phase II study of ramucirumab and erlotinib in treatment-naïve non-small cell lung cancer patients with EGFR mutation and brain metastases (SPIRAL-BRAIN study)

Transl Lung Cancer Res. 2023 Aug 30;12(8):1802-1806. doi: 10.21037/tlcr-23-109. Epub 2023 Aug 14.

Authors

Ryo Sawada¹, Naoya Nishioka^{1

2}, Young Hak Kim¹, Fumiaki Kiyomi³, Junji Uchino^{1

4}, Koichi Takayama¹

Affiliations

¹ Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
² Department of Respiratory Medicine, Fukuchiyama City Hospital, Kyoto, Japan.
³ Department of Statistics and Data Center, Clinical Research Support Center Kyushu, Fukuoka, Japan.
⁴ Department of Internal Medicine, Bannan Central Hospital, Shizuoka, Japan.

Abstract

Background: The combination of erlotinib, a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and ramucirumab, an anti-vascular endothelial growth factor receptor (VEGFR) antibody, is one of the most effective treatments for patients with non-small cell lung cancer (NSCLC) and EGFR mutation. However, little is known about the safety and efficacy of this combination treatment for patients with brain metastases.

Methods: This single arm, prospective, open-label, multicenter, phase II study will recruit 32 NSCLC patients with EGFR mutation (except for T790M mutation) and brain metastases (asymptomatic or mild symptoms). Patients will be treated with erlotinib at a dose of 150 mg/body once daily and ramucirumab at a dose of 10 mg/kg once every 2 weeks. The primary endpoint is intracranial overall response rate (iORR) and the secondary endpoints are intracranial disease control rate, intracranial progression-free survival (iPFS), extracranial ORR, extracranial PFS, ORR, overall PFS, overall survival (OS), and safety. The planned number of enrollments was calculated based on a one-sample binomial test (normal approximation) with a two-sided α level of 5% and 80% power, assuming that the expected iORR is 65% and the iORR threshold is 40%.

Discussion: A prospective study to confirm the safety and efficacy of the combined erlotinib plus ramucirumab treatment for NSCLC patients with EGFR mutation and brain metastases is ongoing.

Trial registration: Japan Registry of Clinical Trials, jRCTs051220059.

Keywords: Non-small cell lung cancer (NSCLC); brain metastasis; epidermal growth factor receptor mutation (EGFR mutation); epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI); vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitor (VEGF or VEGFR inhibitor).