Background: EURAMOS is a transAtlantic collaboration formed to improve survival in osteosarcoma by conducting RCTs in a clinically relevant timeframe. EURAMOS-1, the largest study conducted in this rare cancer, has completed accrual. It includes two randomized comparisons investigating treatment optimization on the basis of histological response to neoadjuvant chemotherapy. Methods: Pts ≤40yrs with resectable, high grade extremity or axial osteosarcoma were eligible for registration. All were planned for 2 cycles of neoadjuvant methotrexate, doxorubicin, cisplatin (MAP) then surgical resection of the primary tumour. Pts with complete macroscopic resection and no disease progression were eligible for randomization: [i] “good responders”, <10% viable tumor, MAP +/- 18m maintenance pegylated interferon; [ii] “poor responders”, ≥10% viable tumor, MAP vs MAPIE (MAP + ifosfamide, etoposide). Target sample size was ~1,260 pts randomized requiring ~2000 pts registered estimating a non-randomization rate of 30-35%. Results: From Apr 2005 to Dec 2011, 2,260 pts were registered and 1,332 randomized from 17 countries, 320 sites: median age 14yrs (IQR 11-17); 59% male; 50% femoral site; 23% definite/possible metastases; 92% conventional osteosarcoma (diagnostic biopsy). At Sep 2011 planned IDMC review, neoadjuvant treatment data were known for 2024 pts; 1926 (95%) completed 2 cycles pre-operative MAP with 3 treatment related deaths. 59% pts were randomized; non-consent was the most frequent reason for non-randomization. Relative to expected age-specific incidence (UK NCIN 1979-2007) there was apparent under recruiting of older pts: females ≥15yrs and all pts >19yrs, with greater under recruitment of females than males <35yrs. Pts 20-29yrs were less likely to be randomized than those aged 5-19 and ≥30 yrs, 52% vs 57-62%. Conclusions: EURAMOS-1 demonstrates that large RCTs are feasible in rare cancers with inter-continental collaboration and is a model for future trials. Neoadjuvant MAP was safe in a geographically diverse cohort. Improving clinical trial access and randomization rates for young people is still required. Multiple funders detailed at bit.ly/ymUR9w.