Entry Detail
| General information | |
| Database: | DB00696 |
| Objective: | Thisphase I study evaluated the safe dose, pharmacokinetics, and pharmacodynamics of the aurora kinase A and B inhibitor, PF03814735. |
| Authors: | Sch ffski P, et al |
| Title: | Phase I, openlabel, multicentre, doseescalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF03814735 in advanced solid tumours. |
| Journal: | Eur J Cancer. |
| Year: | 2011 |
| PMID: | 21852114 |
| Trial Design | |
| Clinical Trial Id: | NCT00424632 |
| Agent: | PF03814735 |
| Target: | Serine/threonine protein kinase 12 Aurora kinase A |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase I, openlabel, accelerated doseescalation, PK andPD study |
| Key Patients Feature: | Adults P18 years of age, with radiographic or clinical evidence of advanced or metastatic solid tumours resistant tostandard therapy or for which no standard therapy is available, were eligible for enrolment. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, adequate bone marrow, hepatic, and renal function; and discontinuation of all previous cancer therapies were required.Patients were excluded if they had brain metastases that weresymptomatic and/or required treatment; significant cardiovascular disease within the previous 6 months; or abnormalleft ventricular ejection faction (LVEF) as assessed by echocardiogram or multigated acquisition (MUGA) scan. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients with advanced solid tumours received oral, oncedaily (QD) PF03814735 on Schedule A: days 15 (5100mg); or Schedule B: days 110 (4060mg) of 21day cycles. |
| Primary End Point: | maximum tolerated dose(MTD) and recommendedphase II dose (RP2D) |
| Secondary End Point: | overall safety profile, PK, objective and metabolic tumour response, and modulation of pharmacodynamic (PD) biomarkers in tumours |
| Patients Number: | 57 |
| Trial Results | |
| DLT_MTD: | Doselimitingtoxicities were: febrile neutropenia (Schedule A); and increased levels of aspartate aminotransferase, left ventricular dysfunction, and prolonged lowgrade neutropenia (ScheduleB). Maximum tolerated doses were 80 mg QD (Schedule A) and 50 mg QD (Schedule B). |
| Objective Response Rate: | 19 patients achieved stable disease, including 11/31 (35.5%) patients treated on Schedule A and 8/21 (38.1%) patientson Schedule B. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common treatmentrelated adverse events were mainly mild to moderate and included diarrhoea, fatigue, nausea, and vomiting. |
| Conclusions: | PF03814735 was generally well tolerated with manageable toxicities, and a recommendedphase II dose could be established for both schedules. Aurora B activity was inhibited in tumour tissue, but clinical or metabolic antitumour activity was limited. |