Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors.

Abstract

PURPOSE:

The aim of this study was to investigate the safety and pharmacokinetics of motesanib (AMG 706), a small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and c-Kit in Japanese patients with advanced solid tumors.

METHODS:

Patients were administered motesanib orally once daily (QD) at doses of 50, 100, and 125 mg QD. The total study duration for each patient consisted of three cycles of 28 days per cycle. The primary endpoints were the incidence of dose-limiting toxicities (DLTs), estimation of the maximum tolerated dose (MTD), and assessment of pharmacokinetic parameters of motesanib.

RESULTS:

Fifteen patients were enrolled and received motesanib. No DLTs were observed and, therefore, the MTD was not reached. Motesanib had acceptable toxicity at doses up to 125 mg QD. The pharmacokinetics of motesanib appears to be dose proportional. No objective responses per RECIST were observed. However, all 15 patients achieved stable disease, and five patients had durable (>24 weeks) stable disease.

CONCLUSIONS:

The results of this study demonstrate that motesanib is tolerable in Japanese patients at doses up to 125 mg QD.

• Authors: Yasuhito Fujisaka, Yasuhide Yamada, Noboru Yamamoto, Toshio Shimizu, Yutaka Fujiwara, Kazuhiko Yamada, Tomohide Tamura, Hiroyuki Watanabe, Yu-Nien Sun, Michael B Bass, Mitsuo Seki
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 66 Issue 5 Pg. 935-43 (Oct 2010) ISSN: 1432-0843 [Electronic] Germany
• PMID: 20107802 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Indoles
• Oligonucleotides
• Niacinamide
• imetelstat

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Female
• Humans
• Indoles (administration & dosage, adverse effects, pharmacokinetics)
• Japan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy, pathology)
• Niacinamide (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Oligonucleotides
• Treatment Outcome