Entry Detail
| General information | |
| Database: | DB00559 |
| Objective: | This openlabel, phase I, doseescalation study assessed the maximumtolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib in combination with capecitabine in patients with advanced solid tumors. |
| Authors: | Stheyeney CJ, et al |
| Title: | a phase I study of sunitinib plus capecitabine in patients with advanced solid tumors. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20837944 |
| Trial Design | |
| Clinical Trial Id: | NCT00618124 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | sunitinib plus capecitabine |
| Study Type: | openlabel, phase I, doseescalation study |
| Key Patients Feature: | Patients age 18 years with histologically proven advanced solid malignancies for which curative treatment was not available were enrolled. Allpatients were to have received two or fetheyr prior systemic chemotherapyregimens (excluding capecitabine), while any number of prior biologic (excluding antiangiogenic agents) or immunotherapeutic agents were permittedif completed 4 weeks before study entry. Given the possible effect ofsunitinib and capecitabine on hematopoiesis, previous chemotherapy regimens were limited to two or fetheyr to exclude patients with impaired bonemarrow reserve. Biologic/immunotherapeutic agents are less likely to causelongterm impairment of bone marrow reserve; their prior use was not excluded. Eligible patients had an Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1, life expectancy of 12 weeks, andadequate organ function as defined by blood tests (criteria included AST andALT 2.5 upper limit of normal [ULN], total serum bilirubin 1.5 ULN, absolute neutrophil count 1, 500/mL without growth factor support, and serum creatinine 1.5 ULN). Patients with previously treated stablebrain metastases were eligible. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Sunitinib (25, 37.5, or 50 mg) was administered orally once daily on three dosing schedules: 4 weeks on treatment, 2 weeks off treatment (Schedule 4/2); 2 weeks on treatment, 1 week off treatment (Schedule 2/1); and continuous daily dosing (CDD schedule). Capecitabine (825, 1, 000, or 1, 250 mg/m(2)) was administered orally twice daily on days 1 to 14 every 3 weeks for all patients. Sunitinib and capecitabine doses were escalated in serial patient cohorts. |
| Primary End Point: | MTDs |
| Secondary End Point: | safety, antitumor activity, and pharmacokinetics |
| Patients Number: | 73 |
| Trial Results | |
| DLT_MTD: | Grade 3 adverse events included abdominal pain, mucosalinflammation, fatigue, neutropenia, and handfoot syndrome. The MTD for Schedule 4/2 and theCDD schedule was sunitinib 37.5 mg/d plus capecitabine 1, 000 mg/m2 twice per day; the MTD forSchedule 2/1 was sunitinib 50 mg/d plus capecitabine 1, 000 mg/m2 twice per day |
| Objective Response Rate: | Nine partial responses |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3 adverse events included abdominal pain, mucosal inflammation, fatigue, neutropenia, and handfoot syndrome. |
| Conclusions: | The combination of sunitinib and capecitabine resulted in an acceptable safety profile in patients with advanced solid tumors. Further evaluation of sunitinib in combination with capecitabine may be undertaken using the MTD for any of the three treatment schedules. |