Anzup 1302: a Randomised Phase 3 Trial of Accelerated Versus Standard Bep Chemotherapy for Patients with Intermediate and Poor-Risk Metastatic Germ Cell Tumours (P3Bep)

Abstract

Background: Bleomycin, Etoposide, Cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). High-dose chemotherapy and more complex regimens (eg VIP, T-BEP) have failed to improve cure rates and are more toxic. Accelerating regimens of standard chemotherapy by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers where more complex or higher-dose regimens failed. Aim: To determine if accelerated BEP is superior to standard BEP as 1st line chemotherapy for intermediate and poor risk metastatic GCTs. Trial design: Open-label, randomised, stratified 2-arm multicentre, 2 stage, phase 3 clinical trial. The primary endpoint for stage I of the trial (n = 150) is complete response rate, and for the complete trial (n = 500) is progression-free survival (PFS). A sample size of 150 and 500 patients gives >80% power to detect a 20% improvement in response rates and 7% absolute improvement in 2yr PFS, respectively. Participants: Males aged 16-45years with intermediate or poor-risk metastatic GCTs for 1st line chemotherapy. Planned expansion to include children aged 11+ and females. Regimen: Participants are randomised 1:1 to “standard BEP” or “accelerated BEP”: [Table presented] E-Etoposide 100mg/m2 D1-5; P-Cisplatin25mg/m2 D1-5; B-Bleomycin 30000 IU weekly; Peg G-CSF 6mg s/c given on D6 post EP in both arms Assessments: Weekly during BEP. Initial response assessment at 30-day safety assessment. Final response assessment at 6 months from randomisation or after all post-chemotherapy intervention is completed. Follow-up 3-monthly for 2 years from randomisation, then 6-monthly to 5 years, then annually. Tissue and blood collection for translational substudies Current status: In start-up phase or open to recruitment at 25 sites in Australia & New Zealand. International trial groups invited to participate. Email: p3bep@ctc.usyd.edu.au Webstite: http://www.anzup.org.au/ Disclosure: All authors have declared no conflicts of interest.