Rationale and protocol design for the TORG1835/NEXT-SHIP study: a phase II study of carboplatin, etoposide and nintedanib for unresectable limited/extensive disease small cell lung cancer with idiopathic pulmonary fibrosis

Background: Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with small cell lung cancer (SCLC). The pharmacotherapy for SCLC occasionally induces fatal acute exacerbation of comorbid IP, especially in patients with idiopathic pulmonary fibrosis (IPF). Safe and effective pharmacotherapy is of greater importance in patients with SCLC and IPF, because SCLC presents a poor prognosis without systemic treatment. Nintedanib is expected to restrain acute exacerbation and present angiogenesis-inhibiting effects. Methods: The TORG1835/NEXT-SHIP study is the world’s first multi-center, single-arm, phase II trial for unresectable limited or extensive disease SCLC with IPF. The patients receive carboplatin (area under the curve 5, day 1), etoposide (<75 years old: 100 mg/m2; ⩾75 years old: 80 mg/m2; days 1–3), and nintedanib (150 mg twice a day) every 3 weeks for four cycles. After completion or discontinuation of carboplatin plus etoposide, the patients continue nintedanib until the discontinuation criteria are met. The primary endpoint is the incidence of acute exacerbation of IPF at 28 days after last administration of cytotoxic anti-cancer agents. We set an expected value of 5% and a threshold value of 20%. Taking statistical points (a/b errors: 0.05/0.75) and ineligible patients into account, the sample size was set at 33. The key secondary endpoints are time to first acute exacerbation of IPF, overall response rate, progression-free survival, overall survival, and toxicities. Discussion: Because there is no clinical trial for unresectable SCLC with IPF, our study would provide a major impact on clinical practice. Trial registration: Japan Registry of Clinical Trials, jRCTs031190119, registered date: October 18, 2019 – Retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190119