Entry Detail
| General information | |
| Database: | DB00833 |
| Objective: | Thisphase I study evaluated the safety, tolerability and preliminary efficacy of sorafenib combined with vorinostat in patients with solid tumors. |
| Authors: | Dasari A, et al |
| Title: | a phase I study of sorafenib and vorinostat in patients with advanced solid tumors with expanded cohorts in renal cell carcinoma and non small cell lung cancer. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 22415798 |
| 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: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | sorafenib + vorinostat |
| Study Type: | a phase I study |
| Key Patients Feature: | patients with advanced solid tumors with expanded cohorts in renal cell carcinoma and non small cell lung cancer. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with sorafenib 400 mg po bid daily and vorinostat 200400 mg po days 114 of a 21 day cycle to establish the recommendedphase II dose (RP2D). The tolerability and efficacy of the RP2D was further tested in two cohorts of 612 patients each with advanced RCC and non small cell lung cancer. |
| Primary End Point: | RP2D, MDT, DLTs |
| Secondary End Point: | NA |
| Patients Number: | 17 |
| Trial Results | |
| DLT_MTD: | DLTs were determined during the first cycle of each dose level and were defined as any treatmentrelated more than and equal to grade 3 nonhematological toxicity including nausea, vomiting and diarrhea if more than and equal to grade 3 in spite of adequate supportive care, more than and equal to grade 4 hematologic toxicity, or an unplanned interruption of dosing with either drug for more than 14 days before the start of the second cycle.Dose limiting toxicities (DLT) included intolerable grade 2 handfoot syndrome and multiple grade 1 toxicities causing dose interruption for more than 14 days. |
| Objective Response Rate: | NA |
| 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): | DLTs were determined during the first cycle of each dose level and were defined as any treatmentrelated more than and equal to grade 3 nonhematological toxicity including nausea, vomiting and diarrhea if more than and equal to grade 3 in spite of adequate supportive care, more than and equal to grade 4 hematologic toxicity, or an unplanned interruption of dosing with either drug for more than 14 days before the start of the second cycle |
| Conclusions: | Although tolerable in other tumor types, sorafenib 400 mg po bid with vorinostat 300 mg po daily days 114 of a 21day cycle is not tolerable without dose reductionsdelays in RCC and non small cell lung cancer patients. These patients may require lotheyr doses than the RP2D explored within this study. No confirmed responses they were seen but minor responses particularly in RCC they were observed. |