Entry Detail
| General information | |
| Database: | DB00094 |
| Objective: | EGFR and Src are frequently activated in non small cell lung cancer. In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. they conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in non small cell lung cancer. |
| Authors: | Gold KA, et al |
| Title: | a phase I/II study combining erlotinib and dasatinib for non small cell lung cancer. |
| Journal: | Oncologist. |
| Year: | 2014 |
| PMID: | 25170013 |
| Trial Design | |
| Clinical Trial Id: | NCT00826449 |
| 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: | non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | erlotinib+ dasatinib |
| Study Type: | a phase I/II Study |
| Key Patients Feature: | non small cell lung cancer patients |
| Biomarker: | EGFR mutation |
| Biomark Analysis: | Five patients (15%) had partial responses; all had activating EGFR mutations.Epithelialmesenchymal transition markers did not correlate with outcomes. |
| Control Group Info: | single arm |
| Treatment Info: | the phase I 3+3 doseescalation study enrolled patients with solid tumors to determine the MTD. the phase II trial enrolled patients with advanced non small cell lung cancer who had undergone no previous treatments |
| Primary End Point: | MTD, PFS |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results | |
| DLT_MTD: | MTD was 150 mg of erlotinib and 70 mg of dasatinib daily based on 12 patients treated in the phase I portion |
| Objective Response Rate: | No responses were observed inphase I. |
| Disease Control Rate: | The 35 non small cell lung cancer patients treated inphase II had an overall disease control rate of 59% at 6 weeks. Five patients (15%) had partial responses; all had activating EGFR mutations. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 3.3 months. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | The combination of erlotinib and dasatinib is safe and feasible in non small cell lung cancer. The results of this study do not support use of this combination in molecularly unselected non small cell lung cancer. |