Entry Detail
| General information | |
| Database: | DB00542 |
| Objective: | This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinumresistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). |
| Authors: | Ramasubbaiah R, et al |
| Title: | Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group. |
| Journal: | Gynecol Oncol. |
| Year: | 2011 |
| PMID: | 21955480 |
| Trial Design | |
| Clinical Trial Id: | NCT00526799 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | ovarian, primary peritoneal carcinoma |
| Cancer Subtype: | ovarian cancer or primary peritoneal carcinomatosis |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Sorafenib + weekly topotecan |
| Study Type: | a phase I/II open label, single arm; multiinstitutionalinvestigator initiated study |
| Key Patients Feature: | Patients with advanced, histologically documented OC or PPCwho progressed during or recurred within 6 months after platinumbased chemotherapy were eligible. Eligibility included both measurable and detectable disease. Measurable disease was defined according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0)[16]. Patients with nonmeasurable disease could enroll if they hadclinically or radiologically detectable disease and a pretreatmentserum CA125 levelmore than and equal to 2¡Á upper limit of normal (ULN). All patientswere at least 18 years old, had Eastern Cooperative Oncology Group(ECOG) performance status (PS) of 0-1, and life expectancy of atleast 3 months. Eligibility criteria allowed up to three prior cytotoxictherapies, radiation to less than 25% bone marrow, and requiredadequate hematologic, hepatic, and renal function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | 3+3 dose escalation was used forphase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. the phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. |
| Primary End Point: | maximum tolerated dose(phase I) and response rate (phase II) |
| Secondary End Point: | progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. |
| Patients Number: | 16 |
| Trial Results | |
| DLT_MTD: | Grade3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 handfoot syndrome was recorded. |
| Objective Response Rate: | Therewere 5 partialresponses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded duringphase I and 1 duringphase II. One of those PRs occurred in a patient with platinumsensitive disease |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.7 months (95% C.I., 3.0-5.5) |
| Median OS A vs. C: | 14.0 months (95% C.I., 6.4 ¡ª upper limit not estimable) |
| Adverse Event(agent arm): | Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 handfoot syndrome was recorded. |
| Conclusions: | The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC. |