The PACOVAR-trial: a phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer

• Published in: BMC cancer Vol. 11; no. 1; p. 453
• Main Authors: Eichbaum, Michael, Mayer, Christine, Eickhoff, Regina, Bischofs, Esther, Gebauer, Gerhard, Fehm, Tanja, Lenz, Florian, Fricke, Hans-Christian, Solomayer, Erich, Fersis, Nikos, Schmidt, Marcus, Wallwiener, Markus, Schneeweiss, Andreas, Sohn, Christof
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.10.2011; BioMed Central; BMC
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Ovarian Epithelial; Chemotherapy; Clinical trials; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Diagnosis; Drug Resistance, Neoplasm; Drug therapy; Drug therapy, Combination; Female; Health aspects; Humans; Neoplasm Recurrence, Local - drug therapy; Neoplasms, Glandular and Epithelial - drug therapy; Ovarian cancer; Ovarian Neoplasms - drug therapy; Patient outcomes; Pazopanib; Platinum - therapeutic use; Prognosis; Pyrimidines - administration & dosage; Pyrimidines - therapeutic use; Study Protocol; Sulfonamides - administration & dosage; Sulfonamides - therapeutic use; Vascular endothelial growth factor; Germany
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-11-453

The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC. This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject). The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.