Entry Detail
| General information | |
| Database: | DB00197 |
| Objective: | Melanomas harbor aberrations in the cKit gene. They tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring cKit mutations or amplifications. |
| Authors: | Guo J, et al |
| Title: | Phase II, openlabel, singlearm trial of imatinib mesylate in patients with metastatic melanoma harboring cKit mutation or amplification. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21690468 |
| Trial Design | |
| Clinical Trial Id: | NCT00881049 |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma harboring cKit aberrations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II, openlabel, singlearm trial |
| Key Patients Feature: | patients with metastatic melanoma harboring cKit aberrations |
| Biomarker: | cKit aberrations |
| Biomark Analysis: | Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. |
| Control Group Info: | single arm |
| Treatment Info: | Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d. |
| Primary End Point: | progression free survival (PFS) |
| Secondary End Point: | ORR and OS. |
| Patients Number: | 43 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | the median followup time was 12.0 months. The median progression free survival (PFS) was 3.5 months, and the 6month PFS rate was 36.6%;patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P < .001) |
| Median OS A vs. C: | The 1year overall survival (OS) rate was 51.0%.patients who had PR or SD versus disease progression were 15.0 months versus 9.0 months (P =0.036) |
| Adverse Event(agent arm): | Imatinib 400 mg/d was well tolerated;adverse events were generally mild to moderate in severity and were easily managed by dose reduction, dose interruption, or supportive medical treatment. No treatmentrelated deaths were recorded. The imatinib safety profile was similar to previous reports, and the most common adverse events were edema, fatigue, anorexia, nausea, neutropenia, and elevated ALT or AST. For the 15 patients allowed to escalate to the dose 800 mg/d, toxicity was generally intolerable, and adverse events mainly comprised grades 3 to 4 edema, nausea, and vomiting. |
| Conclusions: | Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic cKit aberrations, with an overall response rate of 23.3%. Escalation to 800 mgd could not restore disease control. |