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

Sponsor:	Children's Oncology Group
Collaborators:	National Cancer Institute (NCI) University College London Hospitals
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00134030

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma Surgery

Drug Information available for: Methotrexate Cisplatin Doxorubicin Doxorubicin hydrochloride Etoposide Interferon alfa-2a Interferon alfa-2b Etoposide phosphate Peginterferon Alfa-2b Interferon alfa-n1 Ifosfamide Interferons

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:	2000
Study Start Date:	November 2005
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Maintenance therapy group 1 arm I: Active Comparator 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
Maintenance therapy group 1 arm II: Experimental 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
Maintenance therapy group 2 arm I: Active Comparator 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
Maintenance therapy group 2 arm II: Experimental 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

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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 174 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

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
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:	February 6, 2010
ClinicalTrials.gov Identifier:	NCT00134030 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

localized osteosarcoma
metastatic osteosarcoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Antibiotics, Antineoplastic
Neoplasms, Connective and Soft Tissue
Cisplatin
Therapeutic Uses
Abortifacient Agents
Methotrexate
Growth Inhibitors

Angiogenesis Modulating Agents
Dermatologic Agents
Alkylating Agents
Etoposide
Nucleic Acid Synthesis Inhibitors
Interferon-alpha
Neoplasms by Histologic Type
Growth Substances
Interferons
Osteosarcoma
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Antiviral Agents

ClinicalTrials.gov processed this record on February 08, 2010