Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma
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|ClinicalTrials.gov Identifier: NCT00023998|
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 4, 2013
|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|
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)|
|Official Title:||A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2|
|Study Start Date :||July 2001|
|Primary Completion Date :||November 2005|
|Estimated Study Completion Date :||May 2007|
Experimental: Treatment (combination chemotherapy)
See detailed description.
Drug: doxorubicin hydrochloride
Other Names:Drug: cisplatin
Other Names:Drug: methotrexate
Other Names:Drug: leucovorin calcium
Given IV or orally
Other Names:Biological: filgrastim
Other Names:Procedure: therapeutic conventional surgery
Undergo resectionRadiation: radiation therapy
Other Names:Drug: etoposide
Other Names:Drug: ifosfamide
Other Names:Biological: trastuzumab
Other Names:Other: laboratory biomarker analysis
- 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.
- Response rate [ Time Frame: Up to 6 years ]Will be estimated with a maximum standard error of no more than 8%.
- Event free survival (EFS) [ Time Frame: 3 years ]Will be estimated by the Kaplan-Meier method with a maximum standard error of 8%.
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 ClinicalTrials.gov identifier (NCT number): NCT00023998
|United States, California|
|Children's Oncology Group|
|Arcadia, California, United States, 91006-3776|
|Principal Investigator:||David Ebb||Children's Oncology Group|