Condition category
Cancer
Date applied
24/08/2004
Date assigned
30/09/2004
Last edited
22/09/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Jeremy Whelan

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2004-000242-20

ClinicalTrials.gov number

NCT00134030

Protocol/serial number

N/A

Study information

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

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

Trent Multi-centre Research Ethics Committee, 07/01/2005, ref: 04/MRE04/79

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Phase

Not Applicable

Drug names

Methotrexate, doxorubicin, cisplatin, pegylated interferon alpha, ifosfamide, etoposide

Primary outcome measures

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 trial start date

30/03/2004

Overall trial end date

30/06/2011

Reason abandoned

Eligibility

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 type

Patient

Age group

Mixed

Gender

Both

Target number of participants

1,400

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, Finland, Ireland, New Zealand, Puerto Rico, Switzerland, United States of America

Trial participating centre

The Middlesex Hospital
London
W1T 3AA
United Kingdom

Sponsor information

Organisation

Medical Research Council (UK)

Sponsor details

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

Sponsor type

Government

Website

http://www.mrc.ac.uk

Funders

Funder type

Research organisation

Funder name

European Science Foundation (ESF)

Alternative name(s)

ESF

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

France

Funder name

Clinical Trials Awards and Advisory Committee (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Deutsche Krebshilfe (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Swedish Cancer Society and Nordic Cancer Union (Scandinavian countries)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Childrens Oncology Group (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25421877
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26033801

Publication citations

Additional files

Editorial Notes