Entry Detail
| General information | |
| Database: | DB00098 |
| Objective: | This randomizedphase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR2 (human epidermal growth factor receptor 2/neu; human epidermal growth factor receptor 2), in chemotherapynaive patients with non small cell lung cancer (non small cell lung cancer); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history. |
| Authors: | Ross HJ, et al |
| Title: | Randomizedphase II multicenter trial of two schedules of lapatinib as first or secondline monotherapy in patients with advanced or metastatic non small cell lung cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2010 |
| PMID: | 20215545 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study |
| Key Patients Feature: | pathologically confirmed non small cell lung cancer, either stage IIIB (with malignant effusion) or IV, or recurrent disease. |
| Biomarker: | EGFR gene amplification, human epidermal growth factor receptor 2 mutation |
| Biomark Analysis: | No responses were seen in three patients with EGFR mutations and five with EGFR gene amplification. No mutations in human epidermal growth factor receptor 2 were found. One of two patients with human epidermal growth factor receptor 2 amplification had a 51% decrease in tumor size; however, this response was unconfirmed. |
| Control Group Info: | single arm |
| Treatment Info: | pts were randomized to lapatinib (orally, 1, 500 mg once daily or 500 mg twice daily) until progression or intolerance. |
| Primary End Point: | DLT, MDT |
| Secondary End Point: | NA |
| Patients Number: | 10 |
| Trial Results | |
| DLT_MTD: | MTD of everolimus was 5 mg when administered daily with gefitinib 250 mg. Two patients who were treated at the 10 mg dose level of everolimus experienced DLT, including grade 5 hypotension and grade 3 stomatitis. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Of 75 patients in the nontargeted population, 1 (1.3%) had partial response and 16 (21%) had stable disease of >or=24 weeks. No complete or partial responses were observed in 56 patients in the targeted population; 14 (25%) had stable disease of >or=24 weeks. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Two patients who were treated at the 10 mg dose level of everolimus experienced DLT, including grade 5 hypotension and grade 3 stomatitis. |
| Conclusions: | For further study, everolimus at a dose of 5 mg daily in combination with daily gefitinib 250 mg is recommended. The 2 radiographic responses identified are encouraging. Aphase 2 trial in patients with non small cell lung cancer is under way. |