A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors Journal Article
| Authors: | Feldman, D. R.; Einhorn, L. H.; Quinn, D. I.; Loriot, Y.; Joffe, J. K.; Vaughn, D. J.; Fléchon, A.; Hajdenberg, J.; Halim, A. B.; Zahir, H.; Motzer, R. J. |
| Article Title: | A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors |
| Abstract: | Summary: Background Tivantinib is a selective, small-molecule inhibitor of the MET receptor tyrosine kinase. Preclinical and phase 1 data suggested a possible role for MET in the pathophysiology of germ cell tumors (GCTs) and a potential clinical benefit from tivantinib in patients with these tumors. Methods Men (≥16 years) with relapsed or refractory, histologically confirmed, non-central nervous system GCTs received oral tivantinib 360 mg twice daily in 28-day cycles until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate in the first 4 cycles, with study termination for <2 responses among the first 21 patients. Secondary endpoints included 12-week progression-free survival (PFS), overall survival (OS), and safety. Results Twenty-seven patients were enrolled in 9 months (median age, 32 years). Most patients had tumors with nonseminoma histology (n = 25), and primary tumor sites were testis (n = 24) and mediastinum (n = 3). Among 25 evaluable patients, no objective responses were observed; accrual was halted when the 21st patient became evaluable. Best response was stable disease (n = 5). Median PFS was 1 month, the 12-week PFS rate was 21 %, and median OS was 6 months. Grade 3 or 4 adverse events considered related to study drug included grade 3 pneumonia and grade 3 syncope (n = 1, each). Conclusions Tivantinib was well tolerated but did not demonstrate single-agent activity in patients with relapsed/refractory GCTs. Rapid accrual to this phase 2 trial was achieved in this rare patient population through multicenter collaboration. © 2013 Springer Science+Business Media New York. |
| Keywords: | germ cell tumor; relapsed; met receptor tyrosine kinase; tivantinib; arq 197; met inhibitor |
| Journal Title: | Investigational New Drugs |
| Volume: | 31 |
| Issue: | 4 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2013-08-01 |
| Start Page: | 1016 |
| End Page: | 1022 |
| Language: | English |
| DOI: | 10.1007/s10637-013-9934-y |
| PROVIDER: | scopus |
| PUBMED: | 23417696 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 4 September 2013" - "CODEN: INNDD" - "Source: Scopus" |
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