Entry Detail
| General information | |
| Database: | DB00196 |
| Objective: | Systemic treatment of metastatic melanoma is largely ineffective and alternative approaches are needed. Imatinib mesylate is an oral tyrosine kinase inhibitor that targets bcrAbl, ckit, plateletderived growth factor receptor (PDGFR)alpha, and PDGFRbeta, leading to remarkable clinical responses in several cancers. Signal transduction via ckit, PDGFRalpha, and PDGFRbeta has been demonstrated in malignant melanoma. |
| Authors: | Wyman K, et al |
| Title: | Multicenterphase II trial of highdose imatinib mesylate in metastatic melanoma: significant toxicity with no clinical efficacy. |
| Journal: | Cancer. |
| Year: | 2006 |
| PMID: | 16565971 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II study |
| Key Patients Feature: | Pts with metastatic melanoma |
| Biomarker: | expression of imatinib responsive kinases by immunohistochemistry/staining for ckit/staining for PDGFRalpha and beta. |
| Biomark Analysis: | Paraffinembedded tumor specimens from 15 patients were tested for expression of imatinib responsive kinases by immunohistochemistry. Three tumors had moderate and 5 tumors had theyak staining for ckit. Five tumor samples had theyak staining for PDGFRalpha and beta. |
| Control Group Info: | single arm |
| Treatment Info: | Initially, patients received imatinib at at dose of 400 mg twice orally each day. Based on Simon's optimal design, the study allowed entry of 21 patients; if there were > or = 2 objective responses, accrual would then continue to a total of 41 patients. |
| Primary End Point: | the response rate, response duration, and 6month progression free survival |
| Secondary End Point: | NA |
| Patients Number: | 26 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | No objective clinical responses were noted among the 25 evaluable patients. |
| Disease Control Rate: | No patient was free of disease progression at 6 months. |
| Median Time to Progression: | The median time to progression was 54 days |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | the median overall survival was 200 days. |
| Adverse Event(agent arm): | Patients experienced 29 episodes of Grade 3 and 2 episodes of Grade 4 toxicity (according to National Cancer Institute common toxicity criteria). |
| Conclusions: | Imatinib is an inactive single agent in metastatic melanoma in a population of predominantely pretreated patients. The levels of ckit andor PDGFRalpha, beta expression in the current study were lotheyr than previously reported. Alternative treatment strategies remain a priority for patients with advanced melanoma. |