A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility and safety of treatment assessed using CTC version 2.0
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.
Up to 6 years
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|