EURAMOS 1

Primary objectives

• To examine in a randomized trial, whether the addition of ifosfamide and etoposide (IE) to post-operative chemotherapy with cisplatin, doxorubicin and methotrexate improves event-free survival for patients with resectable osteosarcoma and a poor histological response to 10 weeks of pre-operative chemotherapy.
• To examine in a randomized trial, whether the addition of pegylated interferon α-2b (ifn) as maintenance therapy after post-operative chemotherapy with cisplatin, doxorubicin and methotrexate improves event-free survival for patients with resectable osteosarcoma and a good histological response to 10 weeks of pre-operative chemotherapy.

Secondary objectives: Improvement in the following outcomes:

• Overall survival
• Short-term toxicity
• Long-term toxicity
• Quality of life

Recruitment into the EURAMOS-1 trial has been stopped on 30.06.2011. All new diagnozed patients should be registered in the new opened EURAMOS-registry. The international studygroup recommands until further notice to treat all patients with the standardarm MAP.

The EURAMOS 1 trial is a multimodal therapy of osteosacoma with surgery and pre-and postoperative Chemotherapy.
Surgery will be performed after 10 weeks of pre-operative chemotherapy. Once histological response to pre-operative chemotherapy has been evaluated, patients will be randomized by contacting the relevant trials center. Randomization must be performed within 35 days from date of definitive surgery. Treatment will be allocated using permuted blocks, stratified by group, site of primary tumor and presence of metastases. A third pre-operative course of AP should not be given as this renders the patient ineligible for randomization. It is permissible to administer up to two additional MTX courses and have the patient remain eligible for randomization.

• Histological evidence of high grade osteosarcoma of the extremity or axial skeleton including those arising as second malignancies
• Resectable disease (defined as disease that is amenable or may become amenable to complete and potentially curative resection. Referral to a recognized specialist center may be appropriate)
• Age ≤ 40 years at date of diagnostic biopsy
• Sufficient cardiac function to receive anthracyclines: SF ≥ 28% or EF ≥ 50%
• Registration within 30 days of diagnostic biopsy
• Start chemotherapy within 30 days of diagnostic biopsy
• Patient fit to undergo protocol treatment and follow-up
• Written informed consent

• Unresectable disease, primary or metastatic or both
• Low grade osteosarcoma
• Juxtacortical (periosteal, parosteal) osteosarcoma
• Craniofacial osteosarcoma
• Any previous treatment for osteosarcoma
• Any previous chemotherapy for any disease
• Any other medical condition precluding treatment with protocol chemotherapy (for example HIV, psychiatric disorder etc)
• Pregnant or lactating women