NCT04012619

Anlotinib Hydrochloride Combined With AP in Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer

Safety and Efficacy of Anlotinib Hydrochloride Combined With Pemetrexed Plus Cisplatin/Carboplatin (AP) as First Line Treatment for Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Sichuan University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Anlotinib is a novel oral multitarget tyrosine kinase inhibitor and primary targeted to VEGFR, FGFR, PDGFR and c-Kit. The ALTER-0303 trial showed that patients with advanced non-small cell lung cancer (NSCLC) who received anlotinib as third-line or further therapy had more survival benefit. Pemetrexed plus platinum-based chemotherapy (AP) was long considered as the first line treatment in non-squamous NSCLC patients with negative driver mutation. In this dose exploration study, the primary objective is to establish the safety profile of anlotinib combined with AP in non-squamous NSCLC patients by identifying dose limiting toxicity (DLT), maximum tolerance dose (MTD), the recommended phase II dose, and schedule. Secondary objective includes the assessment of preliminary antitumor effect.

Detailed description

Anlotinib, a new small molecule inhibitor of multiple receptor tyrosine kinases targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit,8,9 has been approved as a third-line treatment for refractory advanced NSCLC by the China Food and Drug Administration (CFDA) on May 9, 2018.10 Previous study in phase II (ALTER0302) trial has shown a better progression-free survival (PFS) in advanced NSCLC patients treated with anlotinib compared those with the placebo (4.8 vs 1.2 months, P\<0.0001).11 In phase III (ALTER0303) trial, both the overall survival (OS) and PFS of advanced NSCLC patients were observed to be significantly longer in the anlotinib group (median, 9.6 and 5.4 months) than the placebo group (median, 6.3 and 1.4 months).12 Moreover, anlotinib also displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential.13,14 For the lack of recommended drugs with exactly therapeutic effect in the third-line treatment of SCC patients, it is worth to further analyze the efficacy and specifically clinical observation indicator of anlotinib in this subtype of NSCLC patients. In this dose exploration study, the primary objective is to establish the safety profile of anlotinib combined with AP in treatment-naive non-squamous NSCLC patients by identifying dose limiting toxicity (DLT), maximum tolerance dose (MTD), the recommended phase II dose, and schedule. Secondary objective includes the assessment of preliminary antitumor effect.

Conditions

• Non-squamous Non-small-cell Lung Cancer
• Anlotinib

Interventions

Type	Name	Description
DRUG	Anlotinib Hydrochloride	Patients receive pemetrexed with cisplatin/carboplatin once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14.

Timeline

• Start date: 2019-04-30
• Primary completion: 2019-11-05
• Completion: 2020-12-30
• First posted: 2019-07-09
• Last updated: 2023-08-03
• Results posted: 2023-08-03

Locations

1 site across 1 country: China