Entry Detail
| General information | |
| Database: | DB00700 |
| Objective: | The toxicities, pharmacokinetics and recommended dose of oral once daily ZK 304709, a novel multitargeted growth inhibitor (MTGI) with activity against cellcycle progression and angiogenesis, was investigated in patients by administration for 14 consecutive days follotheyd by 14 days recovery. |
| Authors: | Scott EN, et al |
| Title: | a phase I dose escalation study of the pharmacokinetics and tolerability of ZK 304709, an oral multitargeted growth inhibitor (MTGI), in patients with advanced solid tumours. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2009 |
| PMID: | 19280191 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | ZK 304709 |
| Target: | Cell division protein kinase 4 Cell division control protein 2 homolog Cell division protein kinase 9 Cell division protein kinase 7 Cell division protein kinase 2 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumours |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I, openlabel, nonrandomized, interindividual dose escalation study |
| Key Patients Feature: | Patients eligible for study were 18 years of age, WHOperformance status (PS) 0-2, with histologically or cytologically conWrmed solid tumours resistant to standard treatments. Patients had to have recovered from the eVects ofprevious surgery or chemotherapy and have a life expectancy of 3 months. All patients required measurabledisease (by Response Evaluation Criteria in Solid Tumours, RECIST) [7] and laboratory parameters within the followingranges: absolute neutrophil count > 1.5 ¡ê 109/l, haemoglobin> 9 g/dl, platelets 100 ¡ê 109/l, aspartate aminotransferaseand alanine aminotransferase . 2.5 ¡ê upper limit of normal (ULN) (. 5.0 ¡ê ULN in presence of liver metastases), serum bilirubin . 1.5 ¡ê ULN, and serum creatinine .1.5 ¡ê ULN. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The starting dose was determined as 1/20th of the MTD of rats as the more sensitive species from preclinical data, based onpresumed 2 m2 patient surface area. Dosing was daily for 14 consecutive days follotheyd by 14 days recovery. Doses could be held or delayed according to protocoldeWned criteria. Dose reduction was not allowed. Dosing continued until disease progression or unacceptable toxicity. |
| Primary End Point: | maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) |
| Secondary End Point: | safety and tolerability, and pharmacokinetic profile. |
| Patients Number: | 37 |
| Trial Results | |
| DLT_MTD: | The most common drugrelated adverseevents were vomiting, diarrhoea and fatigue. |
| Objective Response Rate: | Thirteen patients had stable diseaseas best response as per RECIST criteria. |
| 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): | The most common drugrelated adverse events were vomiting, diarrhoea and fatigue. |
| Conclusions: | There was no increase in exposure to ZK 304709 with dose escalation above 90 mg, and the MTD was not determined. This study illustrates the importance ofphase I pharmacokinetic data to guide dose escalation and drug development. |