P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for individuals aged 11-45 years with intermediate and poor-risk metastatic germ cell tumours (GCTs).

Abstract

TPS524 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard first-line chemotherapy for intermediate and poor-risk metastatic GCT. Accelerating standard chemotherapy regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. It aims to determine the superiority of accelerated BEP versus standard BEP in this setting. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2 stages. The primary endpoint for stage 1 (n = 150) was favourable response; 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 I error rate of 5% to detect an absolute improvement of 21% in the favourable response rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (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 6mg D6 or filgrastim daily. Study assessments occur at 30 days after completing chemotherapy, 6 months from randomization, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies. As of 24 August 2023, 274 participants have been recruited from 23 ANZ sites, 17 UK sites (led by Cambridge Clinical Trials Unit), and 150 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage 1 analysis of safety and activity (response rate) for the 1st 150 patients was reviewed by the IDSMC, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .