Abstract
BackgroundThe 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.Methods/designThis 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).DiscussionThe 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.Trial registrationClinicalTrials.gov: NCT01238770
Highlights
The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor
The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer
Pazopanib is currently being studied in a number of different tumour types; clinical data are published in renal cell carcinoma (Phase III), breast cancer, ovarian cancer, Soft tissue sarcoma (STS), Non small cellular lung cancer (NSCLC), cervical cancer and clinical trials are currently underway in other solid tumours
Summary
About 8,200 women a year in Germany develop a malignant tumour of the ovary. The incidence of ovarian carcinoma has remained unchanged in the last few decades [1]. Metronomic chemotherapy, defined as the frequent administration of low doses of cytotoxic chemotherapy at frequent intervals, suppresses tumor growth in experimental models, possibly by inhibiting angiogenesis by stimulating the release of thrombospondin [7,8,9] These experimental findings are supported by a clinical trial where encouraging activity with minimal toxicity was observed in patients with breast cancer [10]. Pazopanib is currently being studied in a number of different tumour types; clinical data are published in renal cell carcinoma (Phase III), breast cancer, ovarian cancer, STS, NSCLC, cervical cancer and clinical trials are currently underway in other solid tumours It is being evaluated as a monotherapy, in combination with targeted therapies and in combination with cytotoxic chemotherapy. The current 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
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