| General information |
| Database: | DB00618 |
| Objective: | They evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumabna ve, recurrent glioblastoma (GBM) patients in a phase 2, openlabel, single arm trial. |
| Authors: | Reardon DA, et al |
| Title: | Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab na ve, recurrent glioblastoma. |
| Journal: | J Neurooncol |
| Year: | 2011 |
| PMID: | 21986722 |
| Trial Design |
| Clinical Trial Id: | NCT00953121 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | malignant glioma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | carboplatin, irinotecan, and bevacizumab |
| Study Type: | openlabelphase II study |
| Key Patients Feature: | patients were required to have histologic confirmation of WHO grade IV malignant glioma (GBM or gliosarcoma) that progressed after prior radiation and temozolomide therapy. Patients with prior lowgrade glioma were eligible ifhistologic transformation to grade IV malignant glioma was confirmed. Eligible patients were also: at least 18 years of age; had a KPS C70; were on a stable corticosteroid dose forat least 1 week; and had no more than three prior episodes oftumor progression. Additional enrollment criteria included:hematocrit [29%; absolute neutrophil count [ 1, 000 cells/ll; platelet count [ 100, 000 cells/ll; and serum creatinine, aspartate aminotransferase and bilirubin within 1.5 times theinstitutional upper limit of normal. At least 4 weeks betweensurgical resection or chemotherapy, and at least 12 weeksbetween radiotherapy and enrollment were required. Allpatients provided informed consent. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients received carboplatin (area under the plasma curve [AUC] 4 mg/mlmin) on day one, while bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) for patients on CYP3Aenzymeinducing antiepileptics [EIAEDs] and 125 mg/m(2) for patients not on EIAEDs) were administered on days 1 and 14 of every 28day cycle. |
| Primary End Point: | progression free survival at 6 months (PFS6) |
| Secondary End Point: | safety and median overall survival (OS) |
| Patients Number: | 40 |
| Trial Results |
| DLT_MTD: | Grade 4events were primarily hematologic and included neutropeniaand thrombocytopenia in 20 and 10%, respectively. Themost common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. |
| Objective Response Rate: | The primaryendpoint was progression free survival at 6 months (PFS6)and secondary endpoints included safety and medianoverall survival (OS). All patients had progression afterstandard therapy. The median age was 51 years. Sixteenpatients (40%) had a KPS of 90-100, while 27 (68%) wereat first progression |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The PFS6 rate was 46.5% (95% CI: 30.4, 61.0%) |
| Median OS A vs. C: | 8.3 months [95% confidence interval (CI): 5.9, and 10.7 months]. |
| Adverse Event(agent arm): | Grade 4 events were primarily hematologic and included neutropenia and thrombocytopenia in 20 and 10%, respectively. The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. Eleven patients (28%) discontinued study therapy due to toxicity and 17 patients (43%) required dose modification. One patient died due to treatmentrelated intestinal perforation. |
| Conclusions: | The addition of carboplatin and irinotecan to bevacizumab significantly increases toxicity but does not improve antitumor activity to that achieved historically with singleagent bevacizumab among bevacizumabnaive, recurrent GBM patients. |