Entry Detail
| General information | |
| Database: | DB00096 |
| Objective: | Given the importance of SFK signaling in cancer, known cooperation between SFK and epidermal growth factor receptor (EGFR) signaling, and efficacy of EGFR inhibitors, they performed a phase I trial combining dasatinib, an SFK and multikinase inhibitor, with erlotinib, an EGFR inhibitor, in patients with advanced non small cell lung cancer. |
| Authors: | Haura EB, et al |
| Title: | Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20142592 |
| Trial Design | |
| Clinical Trial Id: | NCT00444015 |
| Agent: | dasatinib |
| Target: | Protooncogene tyrosineprotein kinase SRC Abl Protooncogene tyrosineprotein kinase LCK Protooncogene tyrosineprotein kinase Fyn |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | dasatinib + erlotinib |
| Study Type: | a phase I trial of combined erlotinib and dasatinib in patients with non small cell lung cancer. The primary objectives were to determine the safety and tolerability of this combination and recommend a phase II dose. |
| Key Patients Feature: | patients diagnosed of advanced/metastatic (stage III [pleural metastasis] or IV) non small cell lung cancer, previous chemotherapy, progressive and measurable disease defined by the Response Evaluation Criteria in Solid Tumors |
| Biomarker: | plasma VEGF and bFGF |
| Biomark Analysis: | Reductions in plasma VEGF and bFGF were observed, and reductions in VEGF correlated with disease control. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received erlotinib for 1 week before addition of dasatinib; pharmacokinetics were performed after weeks 1 and 2. Four cohorts were examined, including twicedaily and daily dasatinib dosing. Responses were assessed after 8 weeks. |
| Primary End Point: | Responses were assessed after 8 weeks. |
| Secondary End Point: | NA |
| Patients Number: | 34 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | Two partial responses and one bone response were observed, and the disease control rate was 63%. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The main adverse events include GI (diarrhea, anorexia, and nausea), skin rash, cytopenias, pleural effusions, and fatigue. No effect of escalating doses of dasatinib was observed on erlotinib pharmacokinetics. |
| Conclusions: | The combination of erlotinib and dasatinib is tolerable, with adverse effects consistent with the two agents. Disease control and inhibition of plasma angiogenesis markers they were observed. Personalized strategies for deployment of SFK should receive further attention. |