| General information |
| Database: | DB00875 |
| Objective: | Pololike kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; thisphase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours. |
| Authors: | Lin CC, et al |
| Title: | a phase I study of two dosing schedules of volasertib (BI 6727), an intravenous pololike kinase inhibitor, in patients with advanced solid malignancies |
| Journal: | Br J Cancer. |
| Year: | 2014 |
| PMID: | 24755882 |
| Trial Design |
| Clinical Trial Id: | NCT00969553 |
| Agent: | volasertib
|
| Target: | Serine/threonineprotein kinase PLK1
|
| 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 of two dosing schedules |
| Key Patients Feature: | Asian patients with advanced solid tumours |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients were enrolled simultaneously into two 3week schedules of volasertib: a 2h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation follotheyd a 3+3 design. |
| Primary End Point: | MDT, DLTs, PK profile and Aes |
| Secondary End Point: | NA |
| Patients Number: | 59 |
| Trial Results |
| DLT_MTD: | A DLT was defined as the following events: drugrelated neutropenia Common Terminology Criteria for Adverse Events (CTCAE) grade 4 for 7 days or any grade drugrelated febrile neutropenia or neutropenic infection; drugrelated grade 4 thrombocytopenia; or drugrelated grade 3 nonhaematologic toxicity (except untreated nausea, vomiting, or diarrhoea).The MTD was determined based on doselimiting toxicities (DLT) in the first treatment course.MTDs were 300 mg for schedule A and 150 mg for schedule B. |
| Objective Response Rate: | 43.8% in schedule A and 44.4% in schedule B |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 49 days (range, 30-274 days) in schedule A and 56 days (range, 8-499 days) in schedule B. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common all grade and grade 3 AEs, irrespective of relatedness, in schedules A and B were neutropenia, leukopenia, anaemia, and thrombocytopenia (Tables 3 and and4).4). The most common drugrelated AEs (in schedule A and B, respectively) were neutropenia (56.3% and 33.3%), leukopenia (56.3% and 33.3%), thrombocytopenia (62.5% and 14.8%), and anaemia (40.6% and 18.5%). The incidence of drugrelated haematological side effects appeared to be doserelated in both dose schedules. |
| Conclusions: | These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients |