Entry Detail
| General information | |
| Database: | DB00545 |
| Objective: | Antiangiogenic strategies have demonstrated efficacy in epithelial ovarian cancer (EOC). Sorafenib is a novel multitargeted kinase inhibitor with antiangiogenic activity. Gemcitabine has known activity against EOC. a phase 1 clinical trial of this combination suggested activity in ovarian cancer with no doselimiting toxicity. Thisphase 2 study was designed to examine the safety and efficacy of gemcitabine and sorafenib in patients with recurrent EOC. |
| Authors: | theylch SA, et al |
| Title: | Sorafenib in combination with gemcitabine in recurrent epithelial ovarian cancer: a study of the Princess Margaret Hospitalphase II Consortium. |
| Journal: | Int J Gynecol Cancer. |
| Year: | 2010 |
| PMID: | 20847613 |
| 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 carcinoma or primary peritoneal carcinoma |
| Cancer Subtype: | epithelial ovarian carcinoma or primary peritoneal carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Sorafenib + gemcitabine |
| Study Type: | openlabel, singlearmphase II study |
| Key Patients Feature: | Eligible patients for this study had pathologicallyconfirmed EOC or primary peritoneal carcinoma that hadrecurred after, or was refractory to, initial platinumbasedchemotherapy. Patients must have had measurable disease asdefined by the Response Evaluation Criteria in Solid Tumors(RECIST).10 Patients with platinumsensitive disease (defined as platinumfree interval of more than 12 months) wereeligible but must have been retreated with a platinumbasedregimen before study entry. Patients may have received nomore than 3 prior chemotherapy regimens, including firstline(or adjuvant) chemotherapy but no systemic therapy within4 weeks of study entry and no prior treatment with gemcitabine or with inhibitors of angiogenesis. Additional inclusion criteria included age, 18 years or older; life expectancy, more than 12 weeks; and adequate hematologic, hepatic, andrenal function. Patients with borderline tumors or tumors oflow malignant potential were excluded. Patients could havereceived prior radiotherapy provided that 30% or less of bone marrow was irradiated and no radiotherapy was givenwithin 4 weeks of study entry |
| Biomarker: | CA125 |
| Biomark Analysis: | the combination was associated with encouraging rates of prolonged stable disease and CA125 response. |
| Control Group Info: | single arm |
| Treatment Info: | Gemcitabine (1000 mg/m(2) intravenous [IV]) was administered weekly for 7 of 8 weeks in the first cycle, then weekly for 3 weeks of each subsequent 4week cycle. Sorafenib (400 mg p.o. bid) was given continuously. |
| Primary End Point: | objective response rate |
| Secondary End Point: | CA125 response, time to progression, overall survival, and toxicity. |
| Patients Number: | 43 |
| Trial Results | |
| DLT_MTD: | Hematologic toxicity wascommon but manageable. The most common nonhematologic adverse events were handfootsyndrome, fatigue, hypokalemia, and diarrhea. |
| Objective Response Rate: | Two patientshad a partial response ( objective responserate = 4.7%). Ten patients (23.3%) maintained response or stable disease for at least6 months. GCIG CA125 response was 27.9%. |
| Disease Control Rate: | NA |
| Median Time to Progression: | 5.4 months |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 13.0 months |
| Adverse Event(agent arm): | Hematologic toxicity was common but manageable. The most common nonhematologic adverse events were handfoot syndrome, fatigue, hypokalemia, and diarrhea. |
| Conclusions: | This trial of gemcitabine and sorafenib in recurrent EOC did not meet its primary efficacy end point, but the combination was associated with encouraging rates of prolonged stable disease and CA125 response. |