Study design and objectives
toxicity, ovarian cancer, SD
OVARIAN CANCER, GYNECOLOGIC CANCER, DISEASE, RECRUITMENT, SECONDARY, ONCOLOGY
TOPAZ was a multicentre, single arm, prospective, phase I/II study, performed by academic researchers of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) ovarian cancer study group. The phase-I part was conducted within a 21-month recruitment period (increased with 6 months in the first protocol amendment on December 12, 2012 and with 9 months by the second protocol amendment on Mai 27, 2013) at two German gynaecological oncology centres—the Charité University Hospital Berlin and the University Hospital Leipzig. In the phase II conducted within a recruitment period of 30 months (increased with 6 months in the fourth protocol amendment on March 3, 2015, and with 12 months by the fifth protocol amendment on April 13, 2016) participated seven additional German gynaecological oncology centres.The phase I as dose-escalation study had the primary objective to determine the maximum tolerated dose (MTD) of pazopanib by identification of the dose-limiting toxicity (DLT) of the combination of weekly topotecan and pazopanib, while the phase II aimed to analyse toxicity profiles and safety of the combination with a primary endpoint on progression-free survival (PFS) as described per RECIST. Overall survival, response rate (i.e. complete response (CR) and partial response (PR)) and clinical benefit rate (i.e. the sum of CR, PR and stable disease (SD)) evaluated according RECIST-criteria and CA-125 according to Gynecologic Cancer InterGroup (GCIG) criteria, duration of response, time to progression, quality of life as obtained by EORTC-QLQ C30 and OVAR 28 questionnaires were defined as secondary study objectives of the phase II. During the recruiting period the protocol was approved with amendments documenting the changes of pazopanib manufacturer and the marketing authorisation holder for topotecan.