Entry Detail
| General information | |
| Database: | DB00707 |
| Objective: | This study (EGF10004) assessed the safety/tolerability, pharmacokinetics, and clinical activity of daily oral dosing with lapatinib (GW572016) in patients with ErbB1expressing and/or ErbB2overexpressing advancedstage refractory solid tumors. |
| Authors: | Burris HA 3rd, et al |
| Title: | Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 15955900 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I Safety, Pharmacokinetics, and Clinical ActivityStudy |
| Key Patients Feature: | ibility CriteriaPatients enrolled in this study were males or females age 18years or older with a histologicallyconfirmed diagnosis of cancer;had an archived or fresh biopsy that demonstrated expression ofErbB1(positive byimmunohistochemistry[IHC])and/oroverexpression of ErbB2 (2 or 3 by IHC) or that displayed gene amplification of ErbB2 by fluorescence in situ hybridization; hada Karnofsky performance status $ 70%; had a life expectancyof at least 12 weeks; had a hemoglobin concentration $ 9 g/dL(5 mmol/L), an absolute granulocyte count $ 1, 500/mm3(1.5 109/L), a platelet count $ 100, 000/mm3 (100 109/L);and were able to swallow and retain oral medication. |
| Biomarker: | ErbB1expressing and/or ErbB2overexpressing |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were randomly assigned to one of five dose cohorts of lapatinib administered once daily. Pharmacokinetic samples were obtained on days 1 and 20. Clinical response was assessed every 8 weeks. |
| Primary End Point: | (1)safety and tolerability; (2) pharmacokinetics; (3)biologic effects;(4) a biologically active dose range;(5)the clinical activity |
| Secondary End Point: | NA |
| Patients Number: | 67 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 59 of 67 patients were assessable for diseaseassessment. Four patients experienced partial responses Stable disease(SD) was reported in 24 patients |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequently reported drugrelated adverse events were diarrhea (42%) and rash (31%). No grade 4 drugrelated adverse events were reported. Five grade 3 drugrelated toxicities (gastrointestinaleventsandrash)wereexperiencedbyfourpatients.Drugrelatedinterstitialpneumonitisor cardiac dysfunction associated with other ErbBtargeted therapies was not reported. |
| Conclusions: | Lapatinib was well tolerated at doses ranging from 500 to 1,600 mg once daily. Clinical activity was observed in heavily pretreated patients with ErbB1expressing andor ErbB2overexpressing metastatic cancers, including four PRs in patients with trastuzumabresistant breast cancers and prolonged stable disease in 10 patients. |