Entry Detail
| General information | |
| Database: | DB00539 |
| Objective: | This trial compared the efficacy and toxicity of standard firstline treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. |
| Authors: | Hainsworth JD, et al |
| Title: | Paclitaxel/carboplatin with or without sorafenib in the firstline treatment of patients with stage III/IV epithelial ovarian cancer: a randomizedphase II study of the Sarah Cannon Research Institute. |
| Journal: | Cancer Med. |
| Year: | 2015 |
| PMID: | 25556916 |
| 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 cancer |
| Cancer Subtype: | advanced epithelial ovarian cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Paclitaxel/carboplatin with or without sorafenib |
| Study Type: | randomized, multicenter, communitybasedphase IItrial |
| Key Patients Feature: | Eligible patients were women with histologically confirmed stage III or IV epithelial ovarian carcinoma, previously untreated with chemotherapy or radiation therapy.Initial cytoreductive surgery was required. Following surgery, patients were required to have no remaining tumornodules >3 cm, no residual tumor involvement of thebotheyl, and no intestinal obstruction. patients wererequired to have measurable disease (RECIST) or evaluable disease (no measurable disease with elevated CA125level after surgery). Patients with known residual intraabdominal tumor after cytoreductive surgery who hadnormal postoperative CT scans and normal CA125 wereineligible, unless secondlook laparotomy was planned forrestaging. Additional eligibility requirements included:ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1; adequate blood counts (ANC more than and equal to 1500/lL, platelets more than and equal to 100, 000/lL, hemoglobin more than and equal to 9.0 g/dL); adequate liver function (total bilirubin less than and equal to 1.59 upper limits ofnormal [ULN], ALT (alanine aminotransferase) and AST(aspartate aminotransferase) less than and equal to 2.59 ULN, or less than and equal to 59 ULN ifliver metastases present); serum creatinine less than and equal to 1.59 ULN. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | paclitaxel (175 mg/m(2) , 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). |
| Treatment Info: | patients were randomized (1:1) to receive treatment with paclitaxel (175 mg/m(2) , 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). patients were reevaluated for response after completing 6 weeks of treatment (two cycles); responding or stable patients received six cycles of paclitaxel/carboplatin. |
| Primary End Point: | the proportion of patients with PFS at 2 years. |
| Secondary End Point: | NA |
| Patients Number: | 85 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: 15.4 versus 16.3 months |
| Median OS A vs. C: | patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: 2 year survival 76% versus 81%. |
| Adverse Event(agent arm): | The addition of sorafenib added substantially to the toxicity of the regimen; rash, hand-foot syndrome, mucositis, and hypertension were significantly more common in patients treated with sorafenib. |
| Conclusions: | The addition of sorafenib to standard paclitaxelcarboplatin did not improve efficacy and substantially increased toxicity in the firstline treatment of advanced epithelial ovarian cancer. Based on evidence from this study and other completed trials, sorafenib is unlikely to have a role in the treatment of ovarian cancer. |