| General information |
| Database: | DB00611 |
| Objective: | Bevacizumab combined with chemotherapy has recently shown promising efficacy in recurrent highgrade glioma. Phosphatase and tensin homolog (PTEN) mutation in glioblastoma multiforme (GBM) patients causes abnormally high activity of the pathways of Phosphatidylinositide 3kinases (PI3K), Protein Kinase B (AKT), and the mammalian target of rapamycin (mTOR) and is associated with unfavorable prognosis. Temsirolimus, an mTOR inhibitor, has been welltolerated in monotherapy, but with limited effects. The combination of temsirolimus and antibodies to vascular endothelial factor (VEGF) has not yet been investigated, but with the hypothesis that temsirolimus might provide complimentary therapeutic benefit in combination with bevacizumab, they included patients with progressive GBM after bevacizumab in an openphase II stud |
| Authors: | Lassen U, et al |
| Title: | Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. |
| Journal: | Anticancer Res. |
| Year: | 2013 |
| PMID: | 23564811 |
| Trial Design |
| Clinical Trial Id: | NCT00800917 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab and temsirolimus combination therapy |
| Study Type: | an open labelphase II study |
| Key Patients Feature: | age more than and equal to 18 years; performancestatus (PS) 01; histologically proven recurrent GBM; measurabletumor by magnetic ressonance imaging (MRI); previous treatmentwith bevacizumab; more than four weeks since chemotherapy (sixweeks for nitrosoureas or mitomycin C); and normal organ function.Furthermore standard criteria regarding contraceptive use andinformed consent was applied. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first eight weeks and at progression. |
| Primary End Point: | median progression free survival (PFS) |
| Secondary End Point: | radiographic response, overall survival (OS), and safety |
| Patients Number: | 13 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 0/10 patients obtained partial remission (PR). Two out of 10 patients obtained radiological stable disease (SD). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8 weeks |
| Median OS A vs. C: | 15 weeks |
| Adverse Event(agent arm): | side effects were mild, and the most common grade III sideeffect was hypercholesterolaemia (4/10). Other grade III sideeffects included hypertriglyceridaemia (1/10), thrombocytopenia (1/10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). |
| Conclusions: | Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy. |