Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma (EURAMOS-1)
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| ClinicalTrials.gov Identifier: NCT00134030 |
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Recruitment Status :
Completed
First Posted : August 24, 2005
Results First Posted : June 7, 2023
Last Update Posted : June 7, 2023
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Sponsor:
Children's Oncology Group
Collaborators:
National Cancer Institute (NCI)
University College, London
Medical Research Council
Information provided by (Responsible Party):
Babasola (Sola) Popoola, University College, London
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Localized Osteosarcoma Metastatic Osteosarcoma | Drug: Cisplatin Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Ifosfamide Drug: Methotrexate Biological: Peginterferon Alfa-2b Other: Quality-of-Life Assessment Other: Questionnaire Administration Procedure: Therapeutic Conventional Surgery | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1334 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | November 14, 2005 |
| Actual Primary Completion Date : | January 31, 2015 |
| Actual Study Completion Date : | September 30, 2022 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Cisplatin
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Methotrexate Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Procedure: Therapeutic Conventional Surgery Undergo amputation or limb salvage surgery |
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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.
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Drug: Cisplatin
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Methotrexate Given IV
Other Names:
Biological: Peginterferon Alfa-2b Given subcutaneously
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Procedure: Therapeutic Conventional Surgery Undergo amputation or limb salvage surgery |
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Active Comparator: Maintenance therapy group 2 arm I
Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I.
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Drug: Cisplatin
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Methotrexate Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Procedure: Therapeutic Conventional Surgery Undergo amputation or limb salvage surgery |
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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.
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Drug: Cisplatin
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Drug: Methotrexate Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Procedure: Therapeutic Conventional Surgery Undergo amputation or limb salvage surgery |
Primary Outcome Measures :
- Event-free Survival (EFS) [ Time Frame: From date of randomization to date of the event. ]
EFS is defined as time from randomisation to the first of: death, detection of local recurrence or metastasis, progression of metastatic disease, or detection of a secondary malignancy.
EFS will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Follow up per participant will be assessed for up to 10 years. The 3 year EFS is provided as a summary.
Secondary Outcome Measures :
- Percentage of Patients With Overall Survival [ Time Frame: From date of randomization to date of death. ]
Overall survival is time from randomization until death from any cause.
Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Participants will be assessed for up to 10 years. 5 year overall survival is provided as a summary.
- Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Adverse events are assessed for up to 10 years per participant. ]Percentages of patients experiencing grade 3 and 4 adverse events. These will be compared using chi-square tests or Fisher's exact tests where appropriate.
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| Ages Eligible for Study: | 5 Years to 40 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Histologically confirmed high-grade osteosarcoma, including second malignancies
- Localized or metastatic disease
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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
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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
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No patients with any of the following:
- Craniofacial osteosarcoma
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00134030
Locations
Show 218 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
University College, London
Medical Research Council
Investigators
| Principal Investigator: | Neyssa M Marina | Children's Oncology Group |
Study Documents (Full-Text)
Documents provided by Babasola (Sola) Popoola, University College, London:
Documents provided by Babasola (Sola) Popoola, University College, London:
Study Protocol, Statistical Analysis Plan, and Informed Consent Form [PDF] September 6, 2011
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Babasola (Sola) Popoola, Matthew Sydes, Professor of Clinical Trials and Methodology, University College, London |
| ClinicalTrials.gov Identifier: | NCT00134030 |
| Other Study ID Numbers: |
AOST0331/ EURAMOS-1 NCI-2009-01066 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ISRCTN67613327 ( Registry Identifier: ISRCTN ) MRC-BO08 ( Other Identifier: MRC CTU ) MRC-EURAMOS1 ( Other Identifier: MRC CTU ) 06-93 ( Other Identifier: Children's Oncology Group ) CDR0000438714 ( Other Identifier: TBC ) COG-AOST0331 ( Other Identifier: Children's Oncology Group ) EU-20530 ( Other Identifier: TBC ) 2004-000242-20 ( EudraCT Number ) AOST0331 ( Other Identifier: Children's Oncology Group ) AOST0331 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 24, 2005 Key Record Dates |
| Results First Posted: | June 7, 2023 |
| Last Update Posted: | June 7, 2023 |
| Last Verified: | May 2023 |
Additional relevant MeSH terms:
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Osteosarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Sarcoma Interferons Interferon-alpha Interferon alpha-2 Peginterferon alfa-2b Interferon-alfa-1b Cisplatin Doxorubicin Liposomal doxorubicin |
Methotrexate Etoposide Etoposide phosphate Ifosfamide Isophosphamide mustard Podophyllotoxin Antineoplastic Agents Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents |