Entry Detail
| General information | |
| Database: | DB00819 |
| Objective: | The doselimiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. |
| Authors: | Wong KK, et al |
| Title: | a phase I study with neratinib (HKI272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2009 |
| PMID: | 19318484 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | neratinib |
| Target: | mRNA of human epidermal growth factor receptor 2 Vascular endothelial growth factor receptor 2 Epidermal growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study |
| Key Patients Feature: | patients with solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Neratinib was administered orally as a single dose, follotheyd by a 1week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. |
| Primary End Point: | The doselimiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity |
| Secondary End Point: | NA |
| Patients Number: | 73 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.6 months (95% CI: 1.7, 5.6) in patients with breast cancer and 3.5 months (95% CI: 1.2, 9.0) in patients with lung cancer. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events were diarrhea (88%), nausea (64%), fatigue (63%), vomiting (50%), and anorexia (40%). Neratinibrelated adverse events were similar. |
| Conclusions: | The maximum tolerated dose of oncedaily oral neratinib is 320 mg. The most common neratinibrelated toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation. |