Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00023998
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 4, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and kill them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. Phase II trial to study the effectiveness of chemotherapy with or without trastuzumab in treating patients who have metastatic osteosarcoma

Condition or disease Intervention/treatment Phase
Metastatic Osteosarcoma Drug: doxorubicin hydrochloride Drug: cisplatin Drug: methotrexate Drug: leucovorin calcium Biological: filgrastim Procedure: therapeutic conventional surgery Radiation: radiation therapy Drug: etoposide Drug: ifosfamide Biological: trastuzumab Other: laboratory biomarker analysis Phase 2

Detailed Description:


I. Determine the feasibility and safety of trastuzumab (Herceptin) and chemotherapy in patients with HER2-overexpressing (2+ level of expression) metastatic osteosarcoma.

II. Determine the response rate and 3-year event-free survival of patients treated with this regimen.

III. Determine the cardiac toxicity and late effects of this regimen in these patients.

IV. Determine the response rate and 3-year event-free survival of poor-risk patients with HER2-negative tumors treated with chemotherapy without the addition of trastuzumab.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor HER2 status (positive vs negative).

Patients receive induction therapy comprising doxorubicin IV over 20 minutes followed by cisplatin IV over 4 hours on days 1 and 2 of weeks 1 and 6, and methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. Patients also receive leucovorin calcium IV or orally every 6 hours beginning 24 hours after each methotrexate dose and continuing for at least 10 doses until methotrexate levels sufficiently decrease. Within 24-36 hours after completion of induction therapy, patients receive filgrastim (G-CSF) daily until blood counts recover.

Patients undergo resection of any remaining primary tumor and/or metastatic lesions during week 11. Patients who are unable to undergo resection receive radiotherapy between weeks 11 and 17.

Patients receive post-induction therapy comprising doxorubicin IV over 20 minutes on days 1 and 2 of weeks 17, 25, and 29; cisplatin IV over 4 hours on days 1 and 2 of weeks 17 and 25; methotrexate IV over 4 hours on day 1 of weeks 16, 20, 24, 28, 32, and 33; etoposide IV over 1 hour on days 1-5 of weeks 13, 21, and 34; and ifosfamide IV over 4 hours on days 1-5 of weeks 13, 21, 29, and 34. Patients also receive leucovorin calcium and G-CSF as in induction therapy. Patients whose tumors are found to over express HER2 (2+ level of expression) also receive trastuzumab IV over 30-90 minutes once a week for a total of 34 weeks in addition to the chemotherapy regimen.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80 patients (40 patients per stratum) will be accrued for this study within 2.5 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2
Study Start Date : July 2001
Actual Primary Completion Date : November 2005
Study Completion Date : May 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Treatment (combination chemotherapy)
See detailed description.
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

Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV

Biological: filgrastim
Given IV
Other Names:
  • G-CSF
  • Neupogen

Procedure: therapeutic conventional surgery
Undergo resection

Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP

Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Feasibility and safety of treatment assessed using CTC version 2.0 [ Time Frame: Up to 6 years ]
    Descriptive statistics will be utilized to assess feasibility and safety. All toxicities will be carefully monitored. A detailed tabulation of observed toxicities will be made and a qualitative decision on the feasibility will be made.

  2. Response rate [ Time Frame: Up to 6 years ]
    Will be estimated with a maximum standard error of no more than 8%.

  3. Event free survival (EFS) [ Time Frame: 3 years ]
    Will be estimated by the Kaplan-Meier method with a maximum standard error of 8%.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed high-grade osteosarcoma

    • Metastatic
    • Newly diagnosed
  • No osteosarcoma arising in areas of Paget's disease or radiotherapy-induced sarcoma
  • Presenting with at least 1 of the following:

    • Bone metastases with or without lung metastases
    • Bilateral lung metastases (any number of nodules)
    • Unilateral lung metastases with at least 4 nodules
  • Planned resection of either the primary site or a metastatic site of disease after completion of induction therapy
  • Must be currently enrolled on the tumor biology study COG-P9851
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 50-100% (over age 10)
  • Performance status - Lansky 50-100% (age 10 and under)
  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3
  • Bilirubin ≤ 1.5 times normal
  • SGPT ≤ 3 times normal
  • Creatinine ≤ 1.5 times normal
  • Creatinine clearance or glomerular filtration rate ≥ 70 mL/min
  • Shortening fraction ≥ 28% by echocardiogram
  • Ejection fraction ≥ 50% by echocardiogram or MUGA
  • No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction disturbances
  • Normal organ function
  • HIV negative
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No prior chemotherapy
  • No prior radiotherapy
  • See Disease Characteristics

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 identifier (NCT number): NCT00023998

United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: David Ebb Children's Oncology Group

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00023998     History of Changes
Other Study ID Numbers: NCI-2012-01863
U10CA098543 ( U.S. NIH Grant/Contract )
CDR0000068882 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 4, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Dermatologic Agents
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors