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
EudraCT/CTIS number	2004-000242-20
ClinicalTrials.gov number	NCT00134030
Secondary identifying numbers	N/A

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

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

Study website

Contact information

Dr Jeremy Whelan
Scientific

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

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	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
Study acronym	EURAMOS 1
Study hypothesis	Study 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
Condition	Osteosarcoma
Intervention	All 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 type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Methotrexate, doxorubicin, cisplatin, pegylated interferon alpha, ifosfamide, etoposide
Primary outcome measure	Added as of 10/09/2008: Event-free survival
Secondary outcome measures	Added as of 10/09/2008: 1. Overall survival 2. Toxicity as measured by CTCAE v3.0 3. Quality of life
Overall study start date	30/03/2004
Overall study end date	30/06/2011

Eligibility

Participant type(s)	Patient
Age group	Mixed
Sex	Both
Target number of participants	1,400
Participant inclusion criteria	Eligible 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
Participant exclusion criteria	1. 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
Recruitment start date	30/03/2004
Recruitment end date	30/06/2011

Locations

Countries of recruitment

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

Study participating centre

The Middlesex Hospital

London
W1T 3AA
United Kingdom

Sponsor information

Medical Research Council (UK)
Government

c/o Ian Viney
MRC Centre London
Stehenson House
158-160 North Gower Street
London
NW1 2DA
United Kingdom

Website	http://www.mrc.ac.uk
"ROR"	https://ror.org/03x94j517

Funders

Funder type

Research organisation

European Science Foundation (ESF)
Private sector organisation / International organizations

Alternative name(s): ESF
Location: France

Clinical Trials Awards and Advisory Committee (UK)

No information available

Deutsche Krebshilfe (Germany)

No information available

Swedish Cancer Society and Nordic Cancer Union (Scandinavian countries)

No information available

Childrens Oncology Group (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

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

Editorial Notes

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