A randomised trial of the EURopean and AMerican Osteosarcoma Study group to optimize treatment strategies for resectable osteosarcoma based on histological response to pre-operative chemotherapy

ISRCTN ISRCTN67613327
DOI https://doi.org/10.1186/ISRCTN67613327
ClinicalTrials.gov (NCT) NCT00134030
Clinical Trials Information System (CTIS) 2004-000242-20
Protocol serial number N/A
Sponsor Medical Research Council (UK)
Funders European Science Foundation (ESF), Clinical Trials Awards and Advisory Committee (UK), Deutsche Krebshilfe (Germany), Swedish Cancer Society and Nordic Cancer Union (Scandinavian countries), Childrens Oncology Group (USA)
Submission date
24/08/2004
Registration date
30/09/2004
Last edited
19/10/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-treatment-after-surgery-for-people-with-osteosarcoma

Contact information

Dr Jeremy Whelan
Scientific

The Middlesex Hospital
UCL Hospitals NHS Trust
Mortimer Street
London
W1T 3AA
United Kingdom

Study information

Primary study designInterventional
Study designRandomised controlled trial
Secondary study designRandomised controlled trial
Scientific titleA randomised trial of the EURopean and AMerican Osteosarcoma Study group to optimize treatment strategies for resectable osteosarcoma based on histological response to pre-operative chemotherapy
Study acronymEURAMOS 1
Study objectivesStudy hypothesis added as of 10/09/2008:

Primary objectives:
1. To examine, in a randomised controlled 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.
2. To examine, in a randomised controlled trial, whether the addition of interferon-alpha 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:
3. 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 overall survival, short-term toxicity, long-term toxicity and quality of life.
4. 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.
5. To investigate whether biological or clinical correlates to histological response and outcome can be identified.
6. To establish whether this international cooperation in clinical trials for osteosarcoma is feasible.

Please note that the target number of participants has been added as of 10/09/2008.

On 08/02/2011 the overall trial end date was changed from 30/03/2009 to 30/06/2011.
Ethics approval(s)Trent Multi-centre Research Ethics Committee, 07/01/2005, ref: 04/MRE04/79
Health condition(s) or problem(s) studiedOsteosarcoma
InterventionAll patients who are registered on this study will receive pre-operative chemotherapy with MAP for about 10 weeks. Following surgery for the primary tumour, the histological response to pre-operative chemotherapy will be assessed. Good responders (<10% viable tumor) will be randomized to receive either MAP or MAPifn. Poor responders (≥10% viable tumor) will be randomized to receive either MAP or MAPIE.
MAP = methotrexate, doxorubicin and cisplatin
MAPifn = methotrexate, doxorubicin and cisplatin followed by pegylated interferon alpha
MAPIE = methotrexate, doxorubicin, cisplatin, ifosfamide and etoposide
Intervention typeDrug
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Methotrexate, doxorubicin, cisplatin, pegylated interferon alpha, ifosfamide, etoposide
Primary outcome measure(s)

Added as of 10/09/2008:
Event-free survival

Key secondary outcome measure(s)

Added as of 10/09/2008:
1. Overall survival
2. Toxicity as measured by CTCAE v3.0
3. Quality of life

Completion date30/06/2011

Eligibility

Participant type(s)Patient
Age groupMixed
SexAll
Target sample size at registration1400
Key inclusion criteriaEligible patients will be registered, then following assessment of histological response of primary tumor, may be eligible for randomisation.

Patients must fulfill the following criteria for registration into the trial:
1. Histological evidence of high grade osteosarcoma of the extremity or axial skeleton including those arising as second malignancies
2. Resectable disease
3. Aged 40 years or less at date of diagnostic biopsy
4. Registration within 30 days of diagnostic biopsy
5. Start chemotherapy within 30 days of diagnostic biopsy
6. Neutrophils more than or equal to 1.5 x 10^9/L (or white blood cell count [WBC] more than or equal to 3 x 10^9/L if neutrophils are not available) and platelet count more than or equal to 100 x 10^9/L
7. Glomerular Filtration Rate more than or equal to 70 ml/min/1.73 m^2
8. Serum bilirubin more than or equal to 1.5 x Upper Limit of Normal [ULN]
9. Sufficient cardiac function to receive anthracyclines: shortening fraction (SF) more than or equal to 28% or ejection fraction (EF) more than or equal to 50%
10. Adequate performance status (Karnofsky score more than or equal to 60 or World Health Organisation [WHO] less than or equal to two for patients [aged 16 or over], Lansky score more than or equal to 60 [aged under 16]). Patients whose performance status is adversely affected by a pathologic fracture but who are able to undergo treatment are eligible.
11. Patient fit to undergo protocol treatment and follow-up
12. Written informed consent
Key exclusion criteria1. Unresectable disease, primary or metastatic or both
2. Low grade osteosarcoma
3. Juxtacortical (periosteal, parosteal) osteosarcoma
4. Craniofacial osteosarcoma
5. Any previous treatment for osteosarcoma
6. Any previous chemotherapy for any disease
7. Any other medical condition precluding treatment with protocol chemotherapy (for example Human Immunodeficiency Virus [HIV], psychiatric disorder etc.)
8. Pregnant or lactating women

Patients must fulfill the following criteria for randomisation into the trial:
1. Assessment of histological response in primary tumor within 35 days of definitive surgery
2. Exactly two courses of cisplatin and doxorubicin must have been administered before surgery
3. At least two courses and no more than six courses of methotrexate must have been administered before surgery
4. Recovery from prior therapy allowing administration of chemotherapy
5. No progression of metastatic disease or new metastatic disease
6. Macroscopically complete surgical resection of the primary tumor
7. In patients with metastatic disease, complete removal of all metastases or complete removal planned and deemed feasible
8. Age more than or equal to five for patients with good response
9. Essential data collection will be provided
10. Written consent to undergo randomisation
Date of first enrolment30/03/2004
Date of final enrolment30/06/2011

Locations

Countries of recruitment

  • United Kingdom
  • England
  • Austria
  • Belgium
  • Canada
  • Czech Republic
  • Finland
  • Ireland
  • New Zealand
  • Puerto Rico
  • Switzerland
  • United States of America

Study participating centre

The Middlesex Hospital
London
W1T 3AA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/02/2015 Yes No
Results article results 10/07/2015 Yes No
Plain English results No Yes
Study website Study website 11/11/2025 11/11/2025 No Yes

Editorial Notes

19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)

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