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Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
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: August 6, 2014
Last verified: August 2014
  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:


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
Primary Completion Date: October 2013 (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:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
  • assessed using the EORTC QLQ-C30 questionnaire
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:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Biological: peginterferon alfa-2b
Given subcutaneously
Other Names:
  • PEG-IFN alfa-2b
  • pegylated interferon alfa-2b
  • polyethylene glycol IFN-A2b
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
  • assessed using the EORTC QLQ-C30 questionnaire
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:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
  • assessed using the EORTC QLQ-C30 questionnaire
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:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Procedure: therapeutic conventional surgery
Undergo amputation or limb salvage surgery
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Procedure: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
  • assessed using the EORTC QLQ-C30 questionnaire
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00134030

  Show 175 Study Locations
Sponsors and Collaborators
Children's Oncology Group
University College London Hospitals
Investigators
Principal Investigator: Neyssa Marina, MD 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: August 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Cisplatin
Doxorubicin
Etoposide
Ifosfamide
Interferon-alpha
Interferons
Liposomal doxorubicin
Methotrexate
Peginterferon alfa-2b
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014