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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00134030
Ethics application status
Date submitted
22/08/2005
Date registered
24/08/2005
Date last updated
8/06/2018

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
Universal Trial Number (UTN)
Trial acronym
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
Other interventions - 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

Other interventions: 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
Other interventions
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival - Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals.
Timepoint [1] 0 0
From date of randomization to date of the event, assessed up to 10 years
Secondary outcome [1] 0 0
Overall survival - Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals.
Timepoint [1] 0 0
From date of randomization to date of death, assessed up to 10 years
Secondary outcome [2] 0 0
Toxicity as measured by CTCAE v3.0 - Proportions of patients experiencing grade 3 and 4 toxicities will be compared using chi-square tests or Fisher's exact tests where appropriate.
Timepoint [2] 0 0
Up to 10 years
Secondary outcome [3] 0 0
Quality of life
Timepoint [3] 0 0
Up to 3 years

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/mm?

- Neutrophil count ? 1,500/mm?

- WBC ? 3,000/mm?

- 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
Minimum age
5 Years
Maximum age
40 Years
Gender
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
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
Lady Cilento 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 - Hunter Regional Mail Centre
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
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United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
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Arkansas
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United States of America
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California
Country [5] 0 0
United States of America
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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
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Illinois
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United States of America
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Indiana
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United States of America
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Iowa
Country [15] 0 0
United States of America
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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
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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
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Michigan
Country [22] 0 0
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Minnesota
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Mississippi
Country [24] 0 0
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State/province [24] 0 0
Missouri
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Nebraska
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Nevada
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New Jersey
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New Mexico
Country [29] 0 0
United States of America
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New York
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United States of America
State/province [30] 0 0
North Carolina
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United States of America
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North Dakota
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United States of America
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Ohio
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United States of America
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Oklahoma
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Oregon
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Pennsylvania
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United States of America
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South Carolina
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South Dakota
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United States of America
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Tennessee
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Texas
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Utah
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United States of America
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Vermont
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United States of America
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Virginia
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United States of America
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Washington
Country [44] 0 0
United States of America
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West Virginia
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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
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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New Zealand
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Auckland
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New Zealand
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Christchurch
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New Zealand
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Wellington
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Puerto Rico
State/province [57] 0 0
San Juan
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Switzerland
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Bern
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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 Hospitals
Address [2] 0 0
Country [2] 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/show/NCT00134030
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Neyssa 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
Other publications