| General information |
| Database: | DB00621 |
| Objective: | The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, openlabel, singlearm trial was evaluated. |
| Authors: | Reardon DA, et al |
| Title: | Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. |
| Journal: | cancer |
| Year: | 2011 |
| PMID: | 21590689 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| 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 ofWorld Health Organization (WHO) grade 4 malignantglioma (GBM or gliosarcoma) that progressed after priorbevacizumabbased therapy. Patients with prior lowgradeglioma were eligible if histologic transformation to grade4 malignant glioma was confirmed. Eligible patients werealso at least 18 years of age; had a Karnofsky performancestatus (KPS) 70; and were on a stable corticosteroiddose for at least 1 week. Additional enrollment criteriaincluded hematocrit >29%; absolute neutrophil count>1000 cells/ll; platelet count >100, 000 cells/ll; and serum creatinine, aspartate aminotransferase, and bilirubinwithin 1.5 times the institutional upper limit of normal.At least 4 weeks between surgical resection or chemotherapy, and at least 12 weeks between radiotherapy andenrollment were required. All patients provided informedconsent. There were no limits based on either the numberof prior episodes of progression or therapeutic regimensreceived. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/mlmin) on day 1, whereas bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) for patients on CYP3A enzymeinducing antiepileptics [EIAEDs] and 125 mg/m(2) for patients not on EIAEDs) were administered on days 1 and 14 of every 28day cycle. patients were evaluated after each of the first 2 cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, noncompliance, or voluntary withdrawal. |
| Primary End Point: | progression free survival at 6 months (PFS6) |
| Secondary End Point: | safety and median overall survival (OS) |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | The most common grade 3 or 4 events were hematologic andoccurred in 29% of cycles. Nine patients (38%) required dose modification. There were no treatmentrelated deaths. |
| Objective Response Rate: | The median OS was 5.8 months (95% confidence interval [CI], 4.07.0 months)and PFS6 rate was 16% (95% CI, 5.0%32.5%). |
| Disease Control Rate: | 0.8 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS6 rate was 16% (95% CI: 5.0, 32.5%) |
| Median OS A vs. C: | 5.8 months (95% confidence interval [CI]: 4.0, 7.0 months) |
| Adverse Event(agent arm): | The most common grade 3 or 4 events were hematologic and occurred in 29% of cycles. Nine patients (38%) required dose modification. There were no treatment related deaths. |
| Conclusions: | Carboplatin, irinotecan, and bevacizumab was associated with modest activity and adequate safety among recurrent GBM patients who progressed on bevacizumab previously. |