Entry Detail
| General information | |
| Database: | DB00576 |
| Objective: | Regorafenib is a novel oral multikinase inhibitor of angiogenic (VEGFR13, TIE2), stromal (PDGFR¦Â, FGFR), and oncogenic kinases (KIT, RET, and RAF). This firstinman, phase I doseescalation study assessed the safety, pharmacokinetic, pharmacodynamic, and efficacy profiles of regorafenib in patients with advanced solid tumors. |
| Authors: | Mross K, et al |
| Title: | a phase I doseescalation study of regorafenib (BAY 734506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22421192 |
| Trial Design | |
| Clinical Trial Id: | NCT01103323 NCT01271712 |
| Agent: | regorafenib |
| Target: | Protooncogene tyrosineprotein kinase receptor ret Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Vascular endothelial growth factor receptor 3 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I, openlabel, nonrandomized, dose-escalating study |
| Key Patients Feature: | Men and women aged 18 years or older with histologically or cytologically confirmed advanced solid tumors thathad progressed after standard therapies (as documented byCT or MRI scan at baseline) were eligible for inclusion in thestudy. Other key inclusion criteria included were an EasternCooperative Oncology Group performance status of 0-2; alife expectancy of 12 weeks or more; and adequate bonemarrow, liver, and renal function. Exclusion criteria included were history of cardiac disease; uncontrolled hypertension; human immunodeficiency virus or active hepatitisB/C; clinically serious infection; serious nonhealing wound, ulcer, or bone fracture; symptomatic metastatic brain ormeningeal tumors (unless the patient was 6 months ormore from definitive therapy, had no evidence of tumorgrowth, and was clinically stable; patients with brain metastases must not be undergoing acute steroid therapy orsteroid taper); any seizure disorder requiring anticonvulsant medication; history of organ allograft; pregnancy orbreastfeeding; major surgery within 4 weeks of the start ofstudy treatment; and evidence or history of coagulationdisorders or thrombosis. |
| Biomarker: | plasma cytokines |
| Biomark Analysis: | Tumor perfusion and plasma cytokine analysis showed biologic activity of regorafenib. |
| Control Group Info: | single arm |
| Treatment Info: | Regorafenib was administered orally for 21 days on/seven days off in repeating cycles, until discontinuation due to toxicity or tumor progression. Adverse events (AE) were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Pharmacokinetic profiles were measured after a single dose and on day 21. Pharmacodynamic and efficacy evaluations included tumor perfusion assessment using dynamic contrastenhanced MRI, plasma cytokines, and tumor response using RECIST (v1.0). |
| Primary End Point: | safety, tolerability, and pharmacokinetics |
| Secondary End Point: | NA |
| Patients Number: | 212 |
| Trial Results | |
| DLT_MTD: | The recommended dose for future studies was determined to be 160 mg daily, with a treatment schedule of 21 days on/seven days off in repeating 28day cycles. |
| Objective Response Rate: | Three of 47 evaluable patients achieved a partial response (renal cell carcinoma, colorectal carcinoma, and osteosarcoma). |
| Disease Control Rate: | 0.66 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common drugrelated grade 3 or 4 AEs were dermatologic AEs (hand-foot skin reaction, rash), hypertension, and diarrhea. |
| Conclusions: | Regorafenib showed an acceptable safety profile and preliminary evidence of antitumor activity in patients with solid tumors. |