Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00023998
First received: September 13, 2001
Last updated: February 1, 2013
Last verified: January 2013

September 13, 2001
February 1, 2013
July 2001
November 2005   (final data collection date for primary outcome measure)
  • Feasibility and safety of treatment assessed using CTC version 2.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    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.
  • Response rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Will be estimated with a maximum standard error of no more than 8%.
  • Event free survival (EFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Will be estimated by the Kaplan-Meier method with a maximum standard error of 8%.
Not Provided
Complete list of historical versions of study NCT00023998 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma
A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2

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

PRIMARY OBJECTIVES:

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Osteosarcoma
  • 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
    • MOAB HER2
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (combination chemotherapy)
See detailed description.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
May 2007
November 2005   (final data collection date for primary outcome measure)

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
Both
up to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00023998
NCI-2012-01863, AOST0121, U10CA098543, CDR0000068882
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: David Ebb Children's Oncology Group
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP