| General information |
| Database: | DB00144 |
| Objective: | Thisphase 1, accelerated titration study assessed the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamic effects of BIBF 1120. |
| Authors: | Mross K, et al |
| Title: | Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2010 |
| PMID: | 20028771 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | BIBF 1120
|
| Target: | VEGFR 13, FGFR 13, PDFGR ¦Á and ¦Â
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an open label, phase I accelerated doseescalation trial |
| Key Patients Feature: | Eligible patients were adults with advanced, nonresectable and/or metastatic measurable solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Twentyfive received 50 to 450 mg once daily and 36 received 150 to 300 mg twice daily in 4week treatment courses interspersed by 1 week of washout. Dynamic contrastenhanced magnetic resonance imaging assessed antiangiogenic effect in 42 patients. |
| Primary End Point: | maximum tolerated dose, safety, pharmacokinetic profile, and pharmacodynamics, Aes |
| Secondary End Point: | NA |
| Patients Number: | 61 |
| Trial Results |
| DLT_MTD: | The majority of doselimiting adverse events of Common Toxicity Criteria grade 3 or 4 were reversible liver enzyme elevations. The maximum tolerated dose was 250 mg of BIBF 1120 for once and twice daily dosing. |
| Objective Response Rate: | NA |
| Disease Control Rate: | One complete and two partial responses occurred in patients with renal cell cancer (n = 2) and colorectal cancer (n = 1). Dynamic contrastenhanced magnetic resonance imaging showed a significant reduction in tumor blood flow in 55% of evaluable patients. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most frequent BIBF 1120related adverse events were mostly mild to moderate (Common Toxicity Criteria grade 12) nausea (68.9%), vomiting (45.9%), and diarrhea (44.3%). |
| Conclusions: | BIBF 1120 dosed continuously displayed a favorable safety and pharmacokinetics profile, and first efficacy signals were observed. Twice daily dosing permitted increased drug exposure without additional toxicity. Two hundred milligrams BIBF 1120 twice daily is the recommended dose forphase II monotherapy studies. |