| General information |
| Database: | DB00838 |
| Objective: | To evaluate the safety, maximumtolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics, and preliminary anticancer activity of ramucirumab (IMC1121B), a fully human immunoglobulin G(1) monoclonal antibody targeting the vascular endothelial growth factor receptor (VEGFR)2. |
| Authors: | Spratlin JL, et al |
| Title: | Phase I pharmacologic and biologic study of ramucirumab (IMC1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor2. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20048182 |
| Trial Design |
| Clinical Trial Id: | NCT00793975 |
| Agent: | ramucirumab
|
| Target: | Vascular endothelial growth factor receptor 2
|
| 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 pharmacologic and biologic study |
| Key Patients Feature: | Patients with advanced solid malignancies refractory to treatment or lacking standard therapeutic options were eligible |
| Biomarker: | The effects of ramucirumab on circulating vascular endothelial growth factorA (VEGFA), soluble VEGFR1 and VEGFR2, tumor perfusion, and vascularity using dynamic contrastenhanced magnetic resonance imaging were assessed. |
| Biomark Analysis: | Serum VEGFA increased 1.5 to 3.5 times above pretreatment values and remained in this range throughout treatment at all dose levels. |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated once weekly with escalating doses of ramucirumab. Blood was sampled for PK studies throughout treatment. |
| Primary End Point: | safety, maximumtolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics, and preliminary anticancer activity |
| Secondary End Point: | NA |
| Patients Number: | 37 |
| Trial Results |
| DLT_MTD: | The MTD was defined as the highest dose level at which less than two patients experienced a DLT in cycle 1. DLT was defined as any grade 4 neutropenia lasting more than 7 days; grade more than and equal to 3 febrile neutropenia, thrombocytopenia, or anemia; or any grade more than and equal to 3 nonhematologic toxicity considered drug related by the investigator. |
| Objective Response Rate: | 45% |
| 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 serious events included hypertension (13.5%), abdominal pain (10.8%), and anorexia, vomiting, increased blood alkaline phosphatase, headache, proteinuria, dyspnea, and DVT (each in 5.4% of patients). |
| Conclusions: | Objective antitumor activity and antiangiogenic effects were observed over a wide range of dose levels, suggesting that ramucirumab may have a favorable therapeutic index in treating malignancies amenable to VEGFR2 inhibition. |