Background Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 is standard 1st line chemotherapy for metastatic GCT categorised as intermediate risk or poor risk. Acceleration of standard regimens by shortening the cycle length improved cure rates in other cancers. We aim to determine the superiority of accelerated BEP versus standard BEP in this setting.
Methods This open label, randomised, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n=150) is complete response (CR); and for stage 2 (n=500) is progression free survival at 2 years (PFS2y). These sample sizes provide >80% power with a two-sided type error rate of 5% to detect an absolute improvement of 25% in the CR rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate-risk or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomised (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily. Study assessments 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies. As of August 2020, 135 participants have been recruited from 25 ANZ sites, 14 UK sites (led by Cambridge Clinical Trials Unit), and 140 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n=76) identified no safety concerns. The stage I analysis is anticipated mid-2021.
This international randomised trial of chemotherapy for intermediate and poor-risk metastatic GCT is the first to include adults and children of both sexes..