| General information |
| Database: | DB00629 |
| Objective: | The authors evaluated a 3week schedule of bevacizumab in patients with recurrent highgrade glioma (HGG). |
| Authors: | Raizer JJ, et al |
| Title: | a phase 2 trial of singleagent bevacizumab given in an every3week schedule for patients with recurrent highgrade gliomas. |
| Journal: | cancer |
| Year: | 2010 |
| PMID: | 20665891 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | malignant glioma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II Trial |
| Key Patients Feature: | Patients with histologically proven HGG (GBM, gliosarcoma, anaplastic astrocytoma [AA], anaplastic oligodendronglioma [AO], oranaplastic oligoastrocytoma [AOA]) were eligible if theirtumors were recurrent or progressive.Patients must have failed on previous radiotherapyand TMZ and must have recovered from the toxic effectsof any previous therapy (4 weeks after previous cytotoxicor biologic therapies, 6 weeks after nitrosoureas, and1 week after noncytotoxic agents). If patients underwentinterstitial brachytherapy or stereotactic radiosurgery, then confirmation of progressive disease based on imagingstudies or pathology was required. Patients were aged 18 years and had a life expectancy >8 weeks and aKarnofsky performance status >60. Adequate bone marrowfunction (white blood cells >3000/lL, absolute neutrophilcount >1500/mm3, platelet count >100, 000/mm3, andhemoglobin >10 mg/dL), liver function (alanine and aspartate aminotransferase levels <3 times the upper limit of normal and bilirubin level <1.5 times the upper limit of normal), and renal function (creatinine <1.5 mg/dL) wererequired before starting therapy. A urine protein:creatinine(UPC) ratio 1.0 at screening or a urine dipstick for proteinuria 2t was required. |
| Biomarker: | Tissue correlates were used to quantify tumor content of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor2 (VEGFR2). |
| Biomark Analysis: | The ratio of tumor VEGFA/VEGFR2 was increased in patients aged >55 years; an increased VEGFA/VEGFR2 ratio was correlated nonsignificantly with decreased survival (P =0.052). |
| Control Group Info: | single arm |
| Treatment Info: | Patients received bevacizumab 15 mg/kg every 3 weeks and were evaluated every 6 weeks until tumor progression. |
| Primary End Point: | PFS6 |
| Secondary End Point: | NA |
| Patients Number: | 61 |
| Trial Results |
| DLT_MTD: | The toxicities observed were primarilygrade 1 and 2, and the most common were fatigue, hypertension, and headache. One grade 2 intratumoral bleedand 1 botheyl perforation were reported. |
| Objective Response Rate: | The bestresponse included a partial response in 15 patients (24.5%) and stable disease in 31 patients (50.8%) patients |
| Disease Control Rate: | 0.753 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 10.8 weeks |
| Median OS A vs. C: | 25.6 weeks |
| Adverse Event(agent arm): | The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. One grade 2 intratumoral bleed and 1 botheyl perforation were reported. |
| Conclusions: | An every3week schedule of bevacizumab had antitumor activity and was relatively nontoxic for patients with recurrent HGG. The predictive value of VEGFAVEGFR2 in tumor will require validation in a larger patient cohort. |