Entry Detail
| General information | |
| Database: | DB00974 |
| Objective: | This study evaluated the safety, maximum tolerated dose, pharmacokinetics, and antitumor activity of sorafenib, a multikinase inhibitor, combined with paclitaxel and carboplatin in patients with solid tumors |
| Authors: | Flaherty KT, et al |
| Title: | a phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. |
| Journal: | Clin Cancer Res. |
| Year: | 2008 |
| PMID: | 18676756 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | sorafenib+ carboplatin + paclitaxel |
| Study Type: | a phase I trial |
| Key Patients Feature: | patients with advanced cancer (24 with melanoma) |
| Biomarker: | Pretreatment tumor samples from 17 melanoma patients were analyzed for BRAF mutations. |
| Biomark Analysis: | There was no correlation between BRAF mutational status and treatment responses in patients with melanoma |
| Control Group Info: | single arm |
| Treatment Info: | pts received oral sorafenib 100, 200, or 400 mg twice daily on days 2 to 19 of a 21day cycle. All patients received carboplatin corresponding to AUC6 and 225 mg/m(2) paclitaxel on day 1. Pharmacokinetic analyses were done for sorafenib on days 2 and 19 of cycle 1 and for paclitaxel on day 1 of cycles 1 and 2. |
| Primary End Point: | safety, maximum tolerated dose, pharmacokinetics, and antitumor activity |
| Secondary End Point: | NA |
| Patients Number: | 39 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 25.60% |
| 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): | the most common of which were hematologic (95%), dermatologic (85%), fatigue (59%), sensory neuropathy (59%), nausea (56%), and arthralgia (26%). Grade 4 neutropenia occurred in 3 patients in the 100 mg twice daily cohort (43%), 1 patient in the 200 mg twice daily cohort (33%), and 20 patients in the 400 mg twice daily cohorts (69%). There were no cases of grade 4 thrombocytopenia. Rashes and plantarpalmar erythema were reported in 71%, 33%, and 59% of the patients in the 100, 200, and 400 mg twice daily cohorts, respectively. Of the 29 patients who received sorafenib 400 mg twice daily, handfoot skin reaction grade more than and equal to 3 was reported in 5 (17%). however, there was no clear dosedependent increment in treatmentrelated adverse events |
| Conclusions: | The recommendedphase II doses are oral 400 mg twice daily sorafenib, carboplatin at an AUC6 dose, and 225 mg/m(2) paclitaxel. The tumor responses observed with this combined regimen in patients with melanoma warrant further investigation. |