Entry Detail
| General information | |
| Database: | DB00608 |
| Objective: | Bevacizumab has provided encouraging results in relapsed glioblastoma multiforme (GBM). Preclinical and clinical investigations also showed that continuous lowdose temozolomide has some antiangiogenic activity. Based on this evidence, a phase II trial was designed to investigate an oral regimen of sorafenib, an oral multikinase inhibitor, and metronomic temozolomide for relapsed GBM. |
| Authors: | Zustovich F, et al |
| Title: | Sorafenib plus daily lowdose temozolomide for relapsed glioblastoma: a phase II study. |
| Journal: | Anticancer Res. |
| Year: | 2013 |
| PMID: | 23898124 |
| Trial Design | |
| Clinical Trial Id: | in the EUDRACT Register(registration code 200800176311) |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Sorafenib plus daily lowdose temozolomide |
| Study Type: | a phase II Study |
| Key Patients Feature: | age of 18 years or older, priorhistological diagnosis of GBM (World Health Organization grade IV), documented radiological relapse during or after firstline treatment with radiotherapy plus temozolomide, the presence ofevaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) , Eastern Cooperative Oncology Groupperformance status (ECOG PS) 2 or less, life expectancy longerthan eight weeks, adequate renal function [creatinine level less than1.25times normal value (NV)], adequate liver function [totalbilirubin less than 1.5 the times NV, serum glutamicoxaloacetictransaminase (SGOT) and serum glutamicpyruvic transaminase(SGPT) less than 3times NV], adequate bone marrow reserve[white blood cell count higher than 3000/¦Ìl, platelet count higherthan 100, 000/¦Ìl, hemoglobin level higher than 10 g/dl, internationalnormalized ratio less than 1.5, and activated partial thromboplastintime (aPTT) less than 1.5times NV], and written informed consent. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients (median age=60.0 years) naive for antiangiogenic agents received 400 mg sorafenib twice daily plus TMZ 40 mg/m(2)/day until disease progression. |
| Primary End Point: | the percentage of patients not progressing within 6 months from the start of treatment. |
| Secondary End Point: | NA |
| Patients Number: | 43 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 0.55 |
| Median Time to Progression: | 3.2 months |
| Median PFS A vs. C: | 6month progression free survival was 26% |
| Median OS A vs. C: | 7.4 months |
| Adverse Event(agent arm): | mostly grade 12, was manageable. Grade 34 toxicities were handfoot syndrome (n=4), hypertension (n=2), and fatigue (n=3). |
| Conclusions: | This combination of sorafenib and temozolomide was feasible and safe, showing some activity in patients with relapsed GBM. |