| General information |
| Database: | DB00609 |
| Objective: | They hypothesized that vertical blockade of VEGF signaling by combining bevacizumab with sorafenib in patients with recurrent glioblastoma would result in a synergistic therapeutic effect. They also investigated whether VEGF, VEGFR2 and hypoxiainducible factor1¦Á singlenucleotide polymorphisms (SNP), circulating biomarkers of angiogenesis, and MRI markers such as apparent diffusion coefficient (ADC) are correlated with treatment efficacy and/or toxicity. |
| Authors: | Galanis E, et al |
| Title: | Phase II study of bevacizumab in combination with sorafenib in recurrent glioblastoma (N0776): a north central cancer treatment group trial. |
| Journal: | Clin Cancer Res. |
| Year: | 2013 |
| PMID: | 23833308 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab sorafenib
|
| Target: | NA
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab+sorafenib |
| Study Type: | Phase II Study |
| Key Patients Feature: | aged of 18 years or more andhad histologic confirmation of grade 4 astrocytoma atinitial diagnosis or recurrence. They were required tobe on a stable dose of corticosteroids or no corticosteroids for 1 week or more before baseline imaging, tohave had their last chemotherapy treatment 4 weeks ormore before study entry ( 6 weeks for nitrosoureas), and to be 12 weeks or more from completion of radiotherapy. patients were also required to have an EasternCooperative Oncology Group performance score of 0 to2 and adequate hematologic, hepatic, and renal function. All patients were required to sign the respective Institutional Review Boardapproved consent form beforeenrollment. |
| Biomarker: | circulating endothelial cells;circulating biomarkers of angiogenesis;VEGF, VEGFR2, and HIF1a SNP analysis |
| Biomark Analysis: | They identified SNPs in the VEGF and VEGFR2 promoter regions, which were associated with PFS6 (P<0.022). Among molecular markers of angiogenesis, a higher log2 baseline level of stromal cellderived factor1 was associated with PFS6 success (P=0.04). Circulating endothelial cells decreased during treatment with subsequent increase at disease progression (P=0.022). Imaging analysis showed a trend associating ADCL with poor outcome. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received bevacizumab (5 mg/kg every 2 weeks) with sorafenib (200 mg twice a day, weekly, days 15; group A). Due to toxicity, the starting sorafenib dose was subsequently modified to 200 mg every day (group B). |
| Primary End Point: | 6month PFS (PFS6), safety and adverse effects |
| Secondary End Point: | NA |
| Patients Number: | 54 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.9 mo (95% CI: 2.33.6) |
| Median OS A vs. C: | 5.6 months (95% CI 4.7 - 8.2) |
| Adverse Event(agent arm): | most common grade 3/4 toxicities were fatigue (13/54, 24%), hypertension (8/54, 15%), and hypophosphatemia (7/54, 13%). Sorafenib dose significantly impacted treatment tolerance: 26.3% (5/19 patients) theynt off study due to toxicity and 15.7% (3/19) due to treatment refusal in group A versus 14.3% (5/35 patients) and 5.7% (2/35) respectively in group B. |
| Conclusions: | The bevacizumabsorafenib combination did not improve outcome of patients with recurrent glioblastoma versus historic bevacizumabtreated controls. Biologic markers of response and resistance to bevacizumab in gliomas they were identified which merit prospective validation. |