Entry Detail
| General information | |
| Database: | DB00544 |
| Objective: | Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie, vascular endothelial growth factor receptor [VEGFR], plateletderived growth factor receptor [PDGFR], Flt3, and cKIT). This study assessed its activity and tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS This openlabel, multiinstitutional, phase II study used a twostage design. |
| Authors: | Matei D, et al |
| Title: | Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a gynecologic oncology group trial. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21098323 |
| Trial Design | |
| Clinical Trial Id: | NCT00093626 |
| 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: | ovarian cancer or primary peritoneal carcinomatosis |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | openlabel, multicenter, twostage, phaseIIstudy |
| Key Patients Feature: | Patients with advanced, histologically documented OC or PPC whoexperienced recurrence within 12 months after platinumbased chemotherapy were eligible. Eligibility included both measurable and nonmeasurabledisease. Measurable disease was defined according to Response EvaluationCriteria in Solid Tumor (RECIST).28 Patients with nonmeasurable diseasecould enroll if they had ascites or pleural effusions attributable to disease, radiologic abnormalities that did not meet RECIST criteria, and a pretreatment serum CA125 level higher than twice the upper limit of normal. Onlypatients with measurable disease were used to formally evaluate the activity ofthe study agent. Patients with nonmeasurable disease enrolled in parallel withpatientswhohadmeasurablediseaseforaslongasthetrialwasopenandwereassesseddescriptivelywiththeintentofgaininginsightintothedistributionofPFS for this subgroup of patients previously not included in GynecologicOncology Group (GOG) trials. All patients were at least 18 years old with aGOGperformancestatusof0to2.Eligibilitycriteriaincludedtherequirementof at least one prior, but no more than two prior, cytotoxic therapy; andadequate hematologic, hepatic, and renal functions. Key exclusion criteriawere prior treatment with sorafenib, history of brain metastases, clinical evidence of small botheyl obstruction, and use of oral anticoagulation. |
| Biomarker: | ERK and bRaf expression in tumors and phosphorylation of ERK (pERK) in peripheralblood lymphocytes (PBLs) |
| Biomark Analysis: | ERK and bRaf were expressed in all tumors. Exploratory analyses indicated that pERK in posttreatment PBL specimens was associated with PFS. |
| Control Group Info: | single arm |
| Treatment Info: | Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens, and they experienced progression within 12 months of platinumbased therapy. Treatment consisted of sorafenib 400 mg orally twice per day. |
| Primary End Point: | progression free survival (PFS) at 6 months and toxicity |
| Secondary End Point: | tumor response and duration of PFS and overall survival. |
| Patients Number: | 73 |
| Trial Results | |
| DLT_MTD: | Significant grade 3 or 4 toxicitiesincluded the following: rash (n 7), handfoot syndrome (n 9), metabolic (n 10), GI (n 3), cardiovascular (n 2), and pulmonary (n 2). |
| Objective Response Rate: | Fourteen survived progression free for at least 6 months (24%; 90% CI, 15%to 35%). Two patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease;30 had progressive disease |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.1 months (95% CI, 1.87 to 3.42 months) |
| Median OS A vs. C: | 16.33 months (95% CI, 11.10 to 22.21 months). |
| Adverse Event(agent arm): | Significant grade 3 or 4 toxicities included the following: rash (n 7), handfoot syndrome (n 9), metabolic (n 10), GI (n 3), cardiovascular (n 2), and pulmonary (n 2). O |
| Conclusions: | Sorafenib has modest antitumor activity in patients with recurrent OC, but the activity was at the expense of substantial toxicity. |