Entry Detail
| General information | |
| Database: | DB00540 |
| Objective: | This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinumsensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC). |
| Authors: | Schwandt A, et al |
| Title: | Randomizedphase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer. |
| Journal: | Invest New Drugs. |
| Year: | 2014 |
| PMID: | 24619298 |
| 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: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | sorafenib alone or + carboplatin/paclitaxel |
| Study Type: | Randomizedphase II trial |
| Key Patients Feature: | Patients (pts.) with histologically documented ovarian cancer, peritoneal cancer, or fallopian tube cancer (EOC) who experienced recurrence after initial therapy and who were considered platinum sensitive were eligible for this trial. Platinumsensitivity was defined as no recurrence or progression within6 months of prior platinum therapy. patients were required tohave measurable disease as defined according to RECIST 1.0criteria [13]. All patients were at least 18 years old with anECOG performance status of 0 to 1. Inclusion criteria requiredadequate hematologic, renal and hepatic laboratory functiontests. Eligibility required at least one prior platinumbasedchemotherapy regimen. Patients with more than two priorcytotoxic therapies were not eligible. patients were not eligible if prior progressive disease occurred on or within 6 monthsof platinumbased therapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were randomized to singleagent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 219) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m(2) (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression. |
| Primary End Point: | efficacy with analysis of response rate (RR) of S and S+C/T therapy. |
| Secondary End Point: | PFS and OS. |
| Patients Number: | 36 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. |
| Disease Control Rate: | 77% vs 96% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p=0.012) |
| Median OS A vs. C: | median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. |
| Adverse Event(agent arm): | Consistent with prior studies, adverse events in the singleagent sorafenib arm were predominantly related to TKI class effects of skin toxicity, including PPE, sorafenib alone, 50 % and with combination chemotherapy, 75 % for all grades. Major gastrointestinal toxicities included nausea 36 % S and 50 % S+C/T; and diarrhea 57 % S and 46 % S+ C/T. Hypertension was mostly grade 1 or 2 occurring 43 % sorafenib alone, and 39 % S+C/T. Fatigue was common in both arms with 57 % of patients in S alone and 64 % S+C/T.As anticipated peripheral neuropathy was experienced by68 % of patients in combination S+C/T compared with nonefor sorafenib alone. Similarly, the S+C/T arm resulted insignificant numbers of all grades of cytopenias with 7 %grades 3 or 4 neutropenia in sorafenib alone and 75 % grades3 or 4 neutropenia in S+C/T. |
| Conclusions: | Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinumsensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; hotheyver, there they were increased grade and frequencies of toxicities. |