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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00134030




Registration number
NCT00134030
Ethics application status
Date submitted
22/08/2005
Date registered
24/08/2005
Date last updated
7/06/2023

Titles & IDs
Public title
Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma
Scientific title
A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-operative Chemotherapy
Secondary ID [1] 0 0
NCI-2009-01066
Secondary ID [2] 0 0
AOST0331/ EURAMOS-1
Universal Trial Number (UTN)
Trial acronym
EURAMOS-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Localized Osteosarcoma 0 0
Metastatic Osteosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Methotrexate
Treatment: Other - Peginterferon Alfa-2b
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration
Treatment: Surgery - Therapeutic Conventional Surgery

Active comparator: Maintenance therapy group 1 arm I - Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29.

Experimental: Maintenance therapy group 1 arm II - Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104.

Active comparator: Maintenance therapy group 2 arm I - Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I.

Experimental: Maintenance therapy group 2 arm II - Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32.


Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Drugs: Methotrexate
Given IV

Treatment: Other: Peginterferon Alfa-2b
Given subcutaneously

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Surgery: Therapeutic Conventional Surgery
Undergo amputation or limb salvage surgery
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Other interventions
Intervention code [4] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS)
Timepoint [1] 0 0
From date of randomization to date of the event.
Secondary outcome [1] 0 0
Percentage of Patients With Overall Survival
Timepoint [1] 0 0
From date of randomization to date of death.
Secondary outcome [2] 0 0
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Timepoint [2] 0 0
Adverse events are assessed for up to 10 years per participant.

Eligibility
Key inclusion criteria
* Histologically confirmed high-grade osteosarcoma, including second malignancies

* Localized or metastatic disease
* The primary tumor must be located in the limbs or axial skeleton, including any of the following sites*:

* Long bone of upper limb
* Short bone of upper limb
* Long bone of lower limb
* Short bone of lower limb
* Vertebral column
* Ribs, sternum, clavicle, or scapula
* Pelvic bones, sacrum, or coccyx
* Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy
* Suitable for neoadjuvant chemotherapy
* Performance status - Lansky 50-100% (for patients under 16 years of age)
* Performance status - Karnofsky 50-100%*
* Performance status - WHO or ECOG 0-2*
* Platelet count = 100,000/mm³
* Neutrophil count = 1,500/mm³
* WBC = 3,000/mm³
* Bilirubin = 1.5 times upper limit of normal
* Creatinine clearance = 70 mL/min
* Creatinine based on age as follows:

* No greater than 1.0 mg/dL (for patients 5 to 10 years of age)
* No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
* No greater than 1.5 mg/dL (for patients over 15 years of age)
* Ejection fraction = 50% by radionuclide angiogram
* Shortening fraction = 28% by echocardiogram
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No known HIV positivity
* No prior chemotherapy for any disease
* Prior radiotherapy for another malignancy allowed
* No prior treatment for osteosarcoma
* No patients with any of the following:

* Craniofacial osteosarcoma
Minimum age
5 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/11/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2022
Sample size
Target
Accrual to date
Final
1334
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Newcastle
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [8] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [9] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2310 - Newcastle
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Illinois
Country [13] 0 0
United States of America
State/province [13] 0 0
Indiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Iowa
Country [15] 0 0
United States of America
State/province [15] 0 0
Kansas
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
State/province [17] 0 0
Louisiana
Country [18] 0 0
United States of America
State/province [18] 0 0
Maine
Country [19] 0 0
United States of America
State/province [19] 0 0
Maryland
Country [20] 0 0
United States of America
State/province [20] 0 0
Massachusetts
Country [21] 0 0
United States of America
State/province [21] 0 0
Michigan
Country [22] 0 0
United States of America
State/province [22] 0 0
Minnesota
Country [23] 0 0
United States of America
State/province [23] 0 0
Mississippi
Country [24] 0 0
United States of America
State/province [24] 0 0
Missouri
Country [25] 0 0
United States of America
State/province [25] 0 0
Nebraska
Country [26] 0 0
United States of America
State/province [26] 0 0
Nevada
Country [27] 0 0
United States of America
State/province [27] 0 0
New Jersey
Country [28] 0 0
United States of America
State/province [28] 0 0
New Mexico
Country [29] 0 0
United States of America
State/province [29] 0 0
New York
Country [30] 0 0
United States of America
State/province [30] 0 0
North Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
North Dakota
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
State/province [33] 0 0
Oklahoma
Country [34] 0 0
United States of America
State/province [34] 0 0
Oregon
Country [35] 0 0
United States of America
State/province [35] 0 0
Pennsylvania
Country [36] 0 0
United States of America
State/province [36] 0 0
South Carolina
Country [37] 0 0
United States of America
State/province [37] 0 0
South Dakota
Country [38] 0 0
United States of America
State/province [38] 0 0
Tennessee
Country [39] 0 0
United States of America
State/province [39] 0 0
Texas
Country [40] 0 0
United States of America
State/province [40] 0 0
Utah
Country [41] 0 0
United States of America
State/province [41] 0 0
Vermont
Country [42] 0 0
United States of America
State/province [42] 0 0
Virginia
Country [43] 0 0
United States of America
State/province [43] 0 0
Washington
Country [44] 0 0
United States of America
State/province [44] 0 0
West Virginia
Country [45] 0 0
United States of America
State/province [45] 0 0
Wisconsin
Country [46] 0 0
Canada
State/province [46] 0 0
Alberta
Country [47] 0 0
Canada
State/province [47] 0 0
British Columbia
Country [48] 0 0
Canada
State/province [48] 0 0
Manitoba
Country [49] 0 0
Canada
State/province [49] 0 0
Newfoundland and Labrador
Country [50] 0 0
Canada
State/province [50] 0 0
Nova Scotia
Country [51] 0 0
Canada
State/province [51] 0 0
Ontario
Country [52] 0 0
Canada
State/province [52] 0 0
Quebec
Country [53] 0 0
Canada
State/province [53] 0 0
Saskatchewan
Country [54] 0 0
New Zealand
State/province [54] 0 0
Auckland
Country [55] 0 0
New Zealand
State/province [55] 0 0
Christchurch
Country [56] 0 0
New Zealand
State/province [56] 0 0
Wellington
Country [57] 0 0
Puerto Rico
State/province [57] 0 0
San Juan
Country [58] 0 0
Switzerland
State/province [58] 0 0
Bern
Country [59] 0 0
Switzerland
State/province [59] 0 0
Geneva
Country [60] 0 0
Switzerland
State/province [60] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University College, London
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
Medical Research Council
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This randomized phase III trial is studying combination chemotherapy followed by surgery and two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to compare how well they work in treating patients with osteosarcoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Biological therapies, such as PEG-interferon alfa-2b, may interfere with the growth of tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed. Giving combination chemotherapy together with PEG-interferon alfa-2b after surgery may kill any remaining tumor cells. It is not yet known whether giving combination therapy together with PEG-interferon alfa-2b is more effective than two different combination chemotherapy regimens alone after surgery in treating osteosarcoma.
Trial website
https://clinicaltrials.gov/study/NCT00134030
Trial related presentations / publications
Hazewinkel AD, Lancia C, Anninga J, van de Sande M, Whelan J, Gelderblom H, Fiocco M. Disease progression in osteosarcoma: a multistate model for the EURAMOS-1 (European and American Osteosarcoma Study) randomised clinical trial. BMJ Open. 2022 Mar 4;12(3):e053083. doi: 10.1136/bmjopen-2021-053083.
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KLB, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PCW, Isakoff MS, Janeway KA, Jurgens H, Kager L, Kuhne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MCG, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. doi: 10.1016/S1470-2045(16)30214-5. Epub 2016 Aug 25.
Whelan JS, Bielack SS, Marina N, Smeland S, Jovic G, Hook JM, Krailo M, Anninga J, Butterfass-Bahloul T, Bohling T, Calaminus G, Capra M, Deffenbaugh C, Dhooge C, Eriksson M, Flanagan AM, Gelderblom H, Goorin A, Gorlick R, Gosheger G, Grimer RJ, Hall KS, Helmke K, Hogendoorn PC, Jundt G, Kager L, Kuehne T, Lau CC, Letson GD, Meyer J, Meyers PA, Morris C, Mottl H, Nadel H, Nagarajan R, Randall RL, Schomberg P, Schwarz R, Teot LA, Sydes MR, Bernstein M; EURAMOS collaborators. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Ann Oncol. 2015 Feb;26(2):407-14. doi: 10.1093/annonc/mdu526. Epub 2014 Nov 24.
Public notes

Contacts
Principal investigator
Name 0 0
Neyssa M Marina
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00134030