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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:
National Cancer Institute (NCI)
University College London Hospitals
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00134030
First received: August 22, 2005
Last updated: August 3, 2012
Last verified: June 2011
History of Changes
  Purpose

RATIONALE: 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.

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.


Condition Intervention Phase
Sarcoma
 Biological: PEG-interferon alfa-2b
Drug: cisplatin
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: methotrexate
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
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 - A Phase III Intergroup Study

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 2300
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
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.
 Drug: cisplatin
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
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.
 Biological: PEG-interferon alfa-2b
Given subcutaneously
Drug: cisplatin
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
Active Comparator: Maintenance therapy group 2 arm I
Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I.
 Drug: cisplatin
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
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.
 Drug: cisplatin
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV
Drug: methotrexate
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 NOTE: * Craniofacial osteosarcoma is not included
  • Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy
  • Suitable for neoadjuvant chemotherapy

PATIENT CHARACTERISTICS:

Age

  • 5 to 40 at diagnostic biopsy

Performance status

  • Lansky 50-100% (for patients under 16 years of age)
  • Karnofsky 50-100%* OR
  • WHO or ECOG 0-2* NOTE: *For patients 16 years of age and over

Life expectancy

  • Not specified

Hematopoietic

  • Platelet count ≥ 100,000/mm³
  • Neutrophil count ≥ 1,500/mm³ OR
  • WBC ≥ 3,000/mm³

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal

Renal

  • Creatinine clearance ≥ 70 mL/min OR

  • 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)

Cardiovascular

  • Ejection fraction ≥ 50% by radionuclide angiogram OR
  • Shortening fraction ≥ 28% by echocardiogram

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for any disease

Endocrine therapy

  • Not specified

Radiotherapy

  • Prior radiotherapy for another malignancy allowed

Surgery

  • Not specified

Other

  • No prior treatment for osteosarcoma
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00134030

  Show 195 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
University College London Hospitals
Investigators
Study Chair: Neyssa M. Marina, MD Stanford University
Investigator: Mark L. Bernstein, MD, FRCPC Hopital Sainte Justine
Study Chair: Mark L. Bernstein, MD, FRCPC Hopital Sainte Justine
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT00134030     History of Changes
Other Study ID Numbers: CDR0000438714, COG-AOST0331, ISRCTN67613327, EU-20530, MRC-EURAMOS1, MRC-BO08, EUDRACT-2004-000242-20
Study First Received: August 22, 2005
Last Updated: August 3, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
localized osteosarcoma
metastatic osteosarcoma

Additional relevant MeSH terms:
Osteosarcoma
Sarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
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 May 21, 2013