P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).

Abstract

TPS4592 Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Accelerating regimens by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and paediatric age groups open to both males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open-label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in RRs and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 yrs with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT:Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF 6mg SC on Day 6; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30-day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 27 sites open in ANZ, 34 patients recruited by February 2017. International collaborations with UK (led by Cambridge Clinical Trials Unit) and US (led by Childrens Oncology Group) confirmed with sites expected to open by early 2017, and more sites sought for stage 2. Funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and previously CINSW. ANZCTR: ACTRN12613000496718. Clinical trial information: NCT02582697.