TY  - JOUR
A1  - Ronellenfitsch, Ulrich
A1  - Dimitrakopoulou-Strauss, Antonia
A1  - Jakob, Jens
A1  - Kasper, Bernd
A1  - Nowak, Kai
A1  - Pilz, Lothar R.
A1  - Attenberger, Ulrike
A1  - Gaiser, Timo
A1  - Egerer, Gerlinde
A1  - Fröhling, Stefan
A1  - Derigs, Hans-Günter
A1  - Schwarzbach, Matthias
A1  - Hohenberger, Peter
T1  - Preoperative therapy with pazopanib in high-risk soft tissue sarcoma : a phase II window-of-opportunity study by the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS)
T2  - BMJ open
N2  - Introduction: For resectable soft tissue sarcoma (STS), radical surgery, usually combined with radiotherapy, is the mainstay of treatment and the only potentially curative modality. Since surgery is often complicated by large tumour size and extensive tumour vasculature, preoperative treatment strategies with the aim of devitalising the tumour are being explored. One option is treatment with antiangiogenic drugs. The multikinase inhibitor pazopanib, which possesses pronounced antiangiogenic effects, has shown activity in metastatic and unresectable STS, but has so far not been tested in the preoperative setting.
Methods and analysis: This open-label, multicentre phase II window-of-opportunity trial assesses pazopanib as preoperative treatment of resectable STS. Participants receive a 21-day course of pazopanib 800 mg daily during wait time for surgery. Major eligibility criteria are resectable, high-risk adult STS of any location, or metachronous solitary STS metastasis for which resection is planned, and adequate organ function and performance status. The trial uses an exact single-stage design. The primary end point is metabolic response rate (MRR), that is, the proportion of patients with >50% reduction of the mean standardised uptake value (SUVmean) in post-treatment compared to pre-treatment fluorodeoxyglucose positron emission tomography CT. The MRR below which the treatment is considered ineffective is 0.2. The MRR above which the treatment warrants further exploration is 0.4. With a type I error of 5% and a power of 80%, the sample size is 35 evaluable patients, with 12 or more responders as threshold. Main secondary end points are histopathological and MRI response, resectability, toxicity, recurrence-free and overall survival. In a translational substudy, endothelial progenitor cells and vascular epithelial growth factor receptor are analysed as potential prognostic and predictive markers.
Ethics and dissemination: Approval by the ethics committee II, University of Heidelberg, Germany (2012-019F-MA), German Federal Institute for Drugs and Medical Devices (61-3910-4038155) and German Federal Institute for Radiation Protection (Z5-22463/2-2012-007).
Trial registration number: NCT01543802, EudraCT: 2011-003745-18; Pre-results.
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37393
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373937
SN  - 2044-6055
N1  - Open Access This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
VL  - 6
IS  - e009558
SP  - 1
EP  - 12
PB  - BMJ Publishing Group
CY  - London
ER  -