The European and American Osteosarcoma Study Group (EURAMOS)

EURAMOS I : Objectives

Primary objectives

In a randomized trial, to examine 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.
In a randomized trial, to examine whether the addition of interferon-a (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

To investigate whether the addition of IE to post-operative therapy for poor responders, and the addition of ifn as maintenance therapy for good responders, leads to an improvement in the following outcomes:

Overall survival
Short-term toxicity
Long-term toxicity
Quality of life
To investigate whether the addition of IE to post-operative therapy for poor responders, and the addition of ifn as maintenance therapy for good responders, leads to an improvement in event-free and overall survival in patients with localized osteosarcoma at entry.
To investigate whether biological or clinical correlates to histological response and outcome can be identified.
To establish whether this international cooperation in clinical trials for osteosarcoma is feasible.
To examine the outcome of the entire cohort of patients.

ELIGIBILITY CRITERIA

Registration eligibility criteria

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
Registration within 30 days of diagnostic biopsy
Start chemotherapy within 30 days of diagnostic biopsy
Neutrophils > 1.5 x 10⁹/L (or WBC > 3 x 10⁹/L if neutrophils are not available) and platelet count > 100 x 10⁹/L
Glomerular Filtration Rate > 70 mL/min/1.73 m²
Serum bilirubin < 1.5 x ULN
Sufficient cardiac function to receive anthracyclines: SF > 28% or EF > 50%
Adequate performance status (Karnofsky score > 60 or WHO < 2 for patients (age > 16), Lansky score > 60 (age < 16). Patients whose performance status is adversely affected by a pathologic fracture but who are able to undergo treatment are eligible (see Appendix A.2 for details)
Patient fit to undergo protocol treatment and follow-up
Written informed consent

Exclusion criteria are as follows:

Randomization eligibility criteria

Assessment of histological response in primary tumor within 35 days of definitive surgery
Two courses of cisplatin and doxorubicin administered before surgery
Between two and six courses of methotrexate administered before surgery
No severe toxicity precluding post-operative treatment
No progression of metastatic disease or new metastatic disease
Macroscopically complete surgical resection of the primary tumor
In patients with metastatic disease, complete removal of all metastases or complete removal planned and deemed feasible
Essential data collection will be provided
Written consent to undergo randomization