P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for individuals aged 11-50 years with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS653 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 is standard first-line chemotherapy for intermediate and poor-risk metastatic GCT. Acceleration of 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 (PFS). 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 PFS (stage 2). The target population is males and females aged 11 to 50 with intermediate-risk or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (3-weekly) or accelerated BEP (2-weekly) with cisplatin 20mg/m 2 D1-5, etoposide 100mg/m 2 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 26 September 2024, 321 participants have been recruited from 21 ANZ sites, 22 UK sites (led by Cambridge Clinical Trials Unit), and 148 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 first 150 patients was reviewed by the Independent Data Safety Monitoring Committee, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .