Entry Detail
| General information | |
| Database: | DB00620 |
| Objective: | They determined the maximum tolerated dose (MTD) and doselimiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, sunitinib, when administered with irinotecan among recurrent malignant glioma (MG) patients. |
| Authors: | Reardon DA, et al |
| Title: | Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21744079 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | malignant glioma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | sunitinib and irinotecan |
| Study Type: | Phase I study |
| Key Patients Feature: | patients were required to have a histologically confirmeddiagnosis of grade III or IV MG that was recurrent. Patientswith prior lowgrade glioma were eligible if histologictransformation to MG prior to enrollment was confirmed.patients were also required to: be C18 years of age; have aKarnofsky performance status (KPS) C70%; be on a stablecorticosteroid dose for C1 week; have satisfactory hematologic (hemoglobin[9 g/dl; absolute neutrophilcount [1, 500 cells/ll; platelet count [100, 000 cells/ll)and biochemical results (serum creatinine and bilirubin B1.59 institutional upper limit of normal [ULN]; andaspartate aminotransferase [AST] and alanine aminotransferase [ALT] B2.59 ULN); have recovered from allexpected toxicity related to previous therapy; and providewritten informed consent. In addition, patients wererequired to be at least 2 weeks from prior surgical resection(1 week for stereotactic biopsy), and 4 weeks from eitherradiotherapy or chemotherapy (6 weeks for nitrosoureas). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | For each 42day cycle, sunitinib was administered once a day for four consecutive weeks followed by a 2 week rest. Irinotecan was administered intravenously every other week. Each agent was alternatively escalated among cohorts of 36 patients enrolled at each dose level. |
| Primary End Point: | MTD, DLTs, PFS and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results | |
| DLT_MTD: | The MTD was 50 mg ofsunitinib combined with 75 mg/m2 of irinotecan. DLTwere primarily hematologic and included grade 4 neutropeniain 3 patients and one patient with grade 4 thrombocytopenia.Nonhematologic DLT included grade 3mucositis (n = 1) and grade 3 dehydration (n = 1). |
| Objective Response Rate: | progression free survival (PFS)6 was 24% and only onepatient achieved a radiographic response |
| Disease Control Rate: | 0.4 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.9 weeks (95% CI: 5.7, 17.7 weeks) |
| Median OS A vs. C: | 53.1 weeks (95% CI: 30.3, 87.9 weeks) |
| Adverse Event(agent arm): | Neutropenia was the most common grade C2 adverse event and affected 13 patients (52%), while fatigue was the next most common toxicity and affected 9 patients (36%), but was grade 2 in seven. The frequency of grade C3 hematologic adverse events was unexpected and affected 12 patients (48%) including eight patients with neutropenia, three patients with thrombocytopenia and one patient with anemia. Grade C2 electrolyte abnormalities were also fairly common and affected 10 patients (40%), and included hypophosphatemia (n = 4), hypocalcemia (n = 2) and hypokalemia (n = 2). Grade C3 amylase/lipase occurred in two patients. Both patients were symptomatic but the event reversed with appropriate medical management. |
| Conclusions: | The combination of sunitinib and irinotecan was associated with moderate toxicity and limited antitumor activity. Further studies with this regimen using the dosing schedules evaluated in this study are not warranted. |