| General information |
| Database: | DB00837 |
| Objective: | In part A, the aim was to define the maximum tolerated dose (MTD) of the hydrogen sulfate (HydSulfate) oral capsule formulation of the mitogenactivated protein kinase kinase inhibitor AZD6244 (ARRY142886). In part B, the aim was to compare the pharmacokinetic profile of the new HydSulfate capsule with the initial AZD6244 freebase suspension and further characterize the pharmacodynamic profile and efficacy of the new formulation. |
| Authors: | Banerji U, et al |
| Title: | The firstinhuman study of the hydrogen sulfate (Hydsulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY142886): a phase I openlabel multicenter trial in patients with advanced cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2010 |
| PMID: | 20179232 |
| Trial Design |
| Clinical Trial Id: | NCT00890825, NCT00890825 |
| Agent: | AZD6244
|
| Target: | Dual specificity mitogenactivated protein kinase kinase
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I openlabel multicenter trial |
| Key Patients Feature: | patients (age >18 y, WHO performance status 02), refractory to standard therapies or for whom no conventional therapies exist, were enrolled from two centers in the Netherlands, one in the United Kingdom, and one in the United States |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | In part A, 30 patients received escalating doses of AZD6244 HydSulfate twice daily. In part B, 29 patients were randomized to a single dose of the HydSulfate capsule or freebase suspension, follotheyd by a washout, then a single dose of the alternative formulation. Patients received the HydSulfate capsule twice daily at MTD of part A thereafter. |
| Primary End Point: | the safety and tolerability. |
| Secondary End Point: | the pharmacokinetics of the HydSulfate capsule following single and multiple oral dosing and (in part B only);pharmacodynamic activity and clinical efficacy. |
| Patients Number: | 59 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| 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 frequently reported AEs, regardless of dose, severity, causality, or seriousness, for the 75mg cohort of parts A and B were fatigue, acneiform dermatitis, nausea, diarrhea, and peripheral edema (Table 2). Time to onset of the most frequently occurring AEs was approximately 29 days for fatigue, 18 days for acneiform dermatitis, 22 days for nausea, 12 days for diarrhea, and 43 days for peripheral edema. Less frequently occurring adverse events are reported in Supplementary Table S1. |
| Conclusions: | The AZD6244 HydSulfate capsule formulation has shown a favorable toxicity, pharmacokinetic, and pharmacodynamic profile, and is being taken forward in ongoing clinical trials. |