Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard first-line chemotherapy for intermediate and poor-risk metastatic GCTs. High-dose chemotherapy and more complex regimens (e.g. VIP, T-BEP) have failed to improve cure-rates. Accelerating regimens of standard chemotherapy by administering them 2-weekly rather than 3-weekly has improved cure-rates in other cancers.
To determine if accelerated BEP is superior to standard BEP as first-line chemotherapy for intermediate and poor-risk metastatic GCTs.
Open-label, randomised, stratified, 2-arm multicentre, 2-stage, phase-3 clinical trial. Primary endpoint for stage I of the trial (n=150) is complete response rate, and for complete trial (n=500) is progression-free-survival (PFS). Sample size of 150 and 500 patients gives >80% power to detect a 20% improvement in response-rate and 7% absolute improvement in 2-year PFS, respectively.
Male and female participants aged 11-45 years with intermediate or poor-risk metastatic GCTs of testis, ovary, retroperitoneum and mediastinum for first-line chemotherapy.
Randomisation 1:1 to “standard BEP” or “accelerated BEP” comprising 4 cycles of: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin IV weekly; and pegylated G-CSF or filgrastim; given every 3-weeks or every 2-weeks respectively. In the accelerated BEP arm, 4 additional weekly doses of bleomycin follow.
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 24-months from randomisation, then 6-monthly for 24-60 months, then annually. Archival tumour-tissue and bloods will be collected for future translational sub-studies.
25-sites open in ANZ by August 2017, 40-patients recruited. 1/19 sites open in UK by August 2017. International collaborations with Ireland and USA (children and adult groups) confirmed with sites expected to open by late 2017.
Co-funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and CINSW. ANZCTR: ACTRN12613000496718.