Entry Detail
| General information | |
| Database: | DB00125 |
| Objective: | A previous clinical trial in the EU and USA indicated that tivozanib at the maximum tolerated dose of 1.5 mg/day showed an antitumor activity in patients with renal cell carcinoma. This Japanesephase I study was designed to determine the recommendedphase II dose of tivozanib for Japanese patients; pharmacokinetic/pharmacodynamic profiles and preliminary efficacy. |
| Authors: | Niwakawa M, et al |
| Title: | Phase I study of highly selective inhibitor of VEGFR tyrosine kinase, tivozanib, in Japanese patients with solid tumors. |
| Journal: | Cancer Sci. |
| Year: | 2013 |
| PMID: | 23679664 |
| Trial Design | |
| Clinical Trial Id: | No: JapicCTI090854. |
| Agent: | tivozanib |
| Target: | VEGF2 receptor Vascular endothelial growth factor receptor 3 Vascular endothelial growth factor receptor 1 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study in the III + III design (Level I, I.0 mg; Level II, I.5 mg) |
| Key Patients Feature: | Japanese patients with advanced solid tumors |
| Biomarker: | plasma VEGF, plasma VEGFR1 and VEGFR2 |
| Biomark Analysis: | Increase of plasma VEGF and decrease of plasma VEGFR1 and VEGFR2 were observed 13 weeks after tivozanib treatment. |
| Control Group Info: | single arm |
| Treatment Info: | Daily treatment with tivozanib in a 3weekson/1weekoff cycle |
| Primary End Point: | phase II dose of tivozanib for Japanese patients |
| Secondary End Point: | pharmacokinetic/pharmacodynamic profiles and preliminary efficacy. |
| Patients Number: | 9 |
| Trial Results | |
| DLT_MTD: | No doselimiting toxicity was observed throughout the study, and the maximum tolerated dose was not reached. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Although no complete or partial response was observed, longterm stable disease continuing more than 170 days was observed in three renal cell carcinoma patients who had failed prior VEGFR inhibitors. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most commonly observed drugrelated adverse events were diarrhea, dysphonia, rash, thyroid stimulating hormone increase, and with severity grade more than and equal to 3, handfoot skin reaction, hypertension, and proteinuria. Those adverse events were generally wellmanageable and mostly resolved within the tolerability evaluation period. |
| Conclusions: | In conclusion, 1.5 mgday of tivozanib in a 3weekson1weekoff setting was tolerable in Japanese patients, and was recommended for further clinical trials in the Japanese population. |