The PARAGON phase 2 trial of anastrozole in women with potentially hormone responsive recurrent/metastatic gynecologic neoplasms.

Abstract

Background: Gynaecological cancers of several pathological subtypes express estrogen and/or progesterone hormone receptors (ER/PR). Previous studies, [all or mostly] retrospective, have reported variable rates of tumour response and clinical benefit. Prospective studies are needed to determine the activity of aromatase inhibitors in women with potentially hormone responsive recurrent gynaecological cancers, and to determine possible predictors of response. Method(s): PARAGON is a Gynecologic Cancer InterGroup phase 2 trial lead by the Australia New Zealand Gynaecological Oncology Group and NHMRC Clinical Trials Centre, in collaboration with Cancer Research UK and the Belgian Gynaecological Oncology Group. The study is designed to facilitate research in rare tumours. The protocol enrols postmenopausal women with recurrent gynaecological cancers of 7 different subtypes: epithelial ovarian cancer (EOC) with only rising CA125 after first line chemotherapy; platinum resistant/refractory EOC; low grade EOC; endometrial carcinomas; endometrial stromal sarcomas; miscellaneous sarcomas; and, granulosa cell and other sex cord stromal tumours. ER/PR positivity must be demonstrated by immunohistochemistry. Each subgroup will enrol 25-50 patients with defined stopping rules based on response and reviewed by an independent data monitoring committee (IDMC). Study treatment is anastrozole 1 mg daily until disease progression or unacceptable toxicity. The primary endpoint is clinical benefit (complete response, partial response, or stable disease at x months). Secondary endpoints include progression free survival, response duration, aspects of QoL, toxicity. Blood and tumour samples are being collected for translational studies and confirmation of ER/PR positivity. Recruitment commenced in 2011 in Australia, New Zealand and the United Kingdom. 236 of 350 planned patients have been enrolled to February 2014. Accrual to the platinum resistant/refractory subgroup closed on 9 December 2013. Anastrozole is being provided by AstraZeneca for study participants in Australia and the UK.