Anlotinib Hydrochloride Combined With AP in Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer
Condition: Non-squamous Non-small-cell Lung Cancer; Anlotinib
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Anlotinib Hydrochloride
Intervention type(s): Drug
Intervention description(s): Patients receive pemetrexed with cisplatin/carboplatin once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14.
Other intervention name(s): Pemetrexed,cisplatin/carboplatin
Intervention MeSH terms: Cisplatin; Carboplatin; Pemetrexed
Intervention model: Sequential Assignment
Intervention model description: The initial dose of anlotinib was set as 12 mg/day with a 2-week on/1-week of schedule. The dose was reduced to 10 mg/day and 8 mg/day in sequence depending on observed DLTs in cycle 1.
Masking: None (Open Label)
Primary purpose: Treatment