Osteosarcoma: Outcome of Therapy Based on Histologic Response. A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma.
N/A
25 Years
Both
Cardiac Toxicity, Sarcoma
Trial Information
Osteosarcoma: Outcome of Therapy Based on Histologic Response. A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma.
OBJECTIVES:
- Determine the rate of in vivo histologic response in patients with osteosarcoma treated
with neoadjuvant cisplatin, methotrexate, and doxorubicin with dexrazoxane (as
cardioprotection).
- Determine the event-free and overall survival of patients with nonmetastatic disease
who show good response to neoadjuvant therapy and receive adjuvant therapy with the
same regimen.
- Determine the event-free survival of patients with nonmetastatic disease who show poor
response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
- Determine the event-free survival and overall survival of patients with metastatic
disease who receive neoadjuvant therapy.
OUTLINE: This is a multicenter study.
- Neoadjuvant therapy: Patients receive neoadjuvant chemotherapy comprising dexrazoxane
IV over 15 minutes, doxorubicin IV over 15 minutes, and cisplatin IV over 4 hours on
days 1 and 2 in week 0. Patients also receive methotrexate IV over 4 hours followed by
leucovorin calcium in weeks 3 and 4. Patients then receive filgrastim (G-CSF)
subcutaneously (SC) once daily beginning 24 hours after completion of chemotherapy and
continuing until blood counts recover. Treatment repeats every 5 weeks for 2 courses in
the absence of disease progression or unacceptable toxicity.
- Surgical resection: Patients undergo definitive surgery in week 11.
- Adjuvant therapy: Patients receive dexrazoxane, doxorubicin, cisplatin, methotrexate,
and leucovorin calcium as in neoadjuvant therapy*. Treatment repeats every 5 weeks for
up to 4 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Cisplatin is not administered in courses 3 and 4 of adjuvant therapy
Patients are followed within 4 weeks, every 3 months for 2 years, every 6 months for 2
years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed osteosarcoma
- No more than 1 month since prior diagnostic biopsy
- Nonmetastatic malignant high-grade osteosarcoma of bone
- Histologically confirmed metastatic disease allowed
- Unresectable primary disease allowed
- No low-grade, parosteal, or periosteal osteosarcoma
PATIENT CHARACTERISTICS:
Age:
- 25 and under
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 8.0 g/dL
Hepatic:
- Bilirubin no greater than 2.0 mg/dL
- ALT less than 5 times normal
Renal:
- Creatinine no greater than 1.5 times normal
- Creatinine clearance or radioisotope glomerular filtration rate greater than 70
mL/min
Cardiovascular:
- Shortening fraction at least 27% by echocardiogram or MUGA
- Ejection fraction at least 45% by echocardiogram or MUGA
Other:
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
- No other concurrent chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
Surgery:
- Not specified
Other:
- No other concurrent therapy with no evidence of progressive disease
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of in vivo histologic response
Safety Issue:
No
Principal Investigator
Ramzi Dagher, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
CDR0000067263
NCT ID:
NCT00019864
Start Date:
March 2000
Completion Date:
Related Keywords:
- Cardiac Toxicity
- Sarcoma
- cardiac toxicity
- localized osteosarcoma
- metastatic osteosarcoma
- recurrent osteosarcoma
- Osteosarcoma
- Sarcoma
Name | Location |
|---|---|
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
| Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital | Houston, Texas 77030-2399 |
