Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma
This study is ongoing, but not recruiting participants.
Sponsor:
Children's Oncology Group
Collaborators:
University College London Hospitals
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00134030
First received: August 22, 2005
Last updated: June 12, 2013
Last verified: June 2013
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Localized Osteosarcoma Metastatic Osteosarcoma |
Drug: doxorubicin hydrochloride Drug: cisplatin Drug: methotrexate Procedure: therapeutic conventional surgery Biological: peginterferon alfa-2b Drug: ifosfamide Drug: etoposide Procedure: quality-of-life assessment Other: questionnaire administration |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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 (IND# 12697) |
Resource links provided by NLM:
MedlinePlus related topics:
Cancer
Drug Information available for:
Methotrexate
Ifosfamide
Interferon
Methotrexate sodium
Cisplatin
Doxorubicin
Doxorubicin hydrochloride
Etoposide
Interferon Alfa-2a
Interferon Alfa-2b
Etoposide phosphate
Peginterferon Alfa-2b
U.S. FDA Resources
Further study details as provided by Children's Oncology Group:
Primary Outcome Measures:
- Event-free survival [ Time Frame: From date of randomization to date of the event, assessed up to 10 years ] [ Designated as safety issue: No ]Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals.
Secondary Outcome Measures:
- Overall survival [ Time Frame: From date of randomization to date of death, assessed up to 10 years ] [ Designated as safety issue: No ]Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals.
- Toxicity as measured by CTCAE v3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]Proportions of patients experiencing grade 3 and 4 toxicities will be compared using chi-square tests or Fisher's exact tests where appropriate.
- Quality of life [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
| Enrollment: | 1164 |
| Study Start Date: | November 2005 |
| Estimated Primary Completion Date: | January 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Maintenance therapy group 1 arm I
Patient undergoes definitive surgery (therapeutic conventional surgery). Patients receive doxorubicin hydrochloride 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 methotrexate (MTX) IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Quality-of-life assessment, prior to start of Cycle 2, after recovery from the doxorubicin of Week 22 Cycle 5, Week 24/Cycle 5, week 72 (18 months after the start of treatment), week 144 (3 years after the start of treatment)
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: methotrexate
Given IV
Other Names:
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
Other: questionnaire administration
Ancillary studies
|
|
Experimental: Maintenance therapy group 1 arm II
Patient undergoes definitive surgery (therapeutic conventional surgery). Patients receive doxorubicin hydrochloride, cisplatin, and high-dose methotrexate (MTX) as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Quality-of-life assessment, prior to start of Cycle 2, after recovery from the doxorubicin of Week 22 Cycle 5, Week 24/Cycle 5, week 72 (18 months after the start of treatment), week 144 (3 years after the start of treatment)
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: methotrexate
Given IV
Other Names:
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Biological: peginterferon alfa-2b
Given subcutaneously
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
Other: questionnaire administration
Ancillary studies
|
|
Active Comparator: Maintenance therapy group 2 arm I
Patient undergoes definitive surgery (therapeutic conventional surgery). Patients receive doxorubicin hydrochloride, cisplatin, and high-dose methotrexate (MTX) as in group 1 arm I. Quality-of-life assessment, prior to start of Cycle 2, after recovery from the doxorubicin of Week 22 Cycle 5, Week 24/Cycle 5, week 72 (18 months after the start of treatment), week 144 (3 years after the start of treatment)
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: methotrexate
Given IV
Other Names:
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
Other: questionnaire administration
Ancillary studies
|
|
Experimental: Maintenance therapy group 2 arm II
Patient undergoes definitive surgery (therapeutic conventional surgery). Patients receive doxorubicin hydrochloride 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 methotrexate (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. Quality-of-life assessment, prior to start of Cycle 2, after recovery from the doxorubicin of Week 22 Cycle 5, Week 24/Cycle 5, week 72 (18 months after the start of treatment), week 144 (3 years after the start of treatment)
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: methotrexate
Given IV
Other Names:
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Drug: ifosfamide
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
Other: questionnaire administration
Ancillary studies
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 5 Years to 40 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00134030
Show 175 Study Locations
Show 175 Study LocationsSponsors and Collaborators
Children's Oncology Group
University College London Hospitals
Investigators
| Principal Investigator: | Neyssa Marina | Children's Oncology Group |
More Information
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00134030 History of Changes |
| Other Study ID Numbers: | AOST0331, NCI-2009-01066, EUDRACT-2004-000242-20, MRC-EURAMOS1, MRC-BO08, ISRCTN67613327, EU-20530, CDR0000438714, COG-AOST0331, U10CA098543 |
| Study First Received: | August 22, 2005 |
| Last Updated: | June 12, 2013 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Osteosarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Sarcoma Interferon-alpha Interferon Alfa-2a Interferon Alfa-2b Interferons Peginterferon alfa-2b Reaferon Methotrexate Etoposide phosphate |
Isophosphamide mustard Cisplatin Doxorubicin Etoposide Ifosfamide Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on June 17, 2013