Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2|
- 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%.
|Study Start Date:||July 2001|
|Estimated Study Completion Date:||May 2007|
|Primary Completion Date:||November 2005 (Final data collection date for primary outcome measure)|
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00023998
|United States, California|
|Children's Oncology Group|
|Arcadia, California, United States, 91006-3776|
|Principal Investigator:||David Ebb||Children's Oncology Group|