Combination Chemotherapy in Treating Patients Undergoing Surgery for Newly Diagnosed High-Grade Osteosarcoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as ifosfamide, methotrexate, cisplatin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery. PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating patients undergoing surgery for newly diagnosed high-grade osteosarcoma.

Detailed Description
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OBJECTIVES: To evaluate the efficacy of a new induction regimen comprising ifosfamide in combination with high-dose methotrexate, cisplatin, and doxorubicin hydrochloride, in terms of clinical response and pathological response of the tumor, in patients with newly diagnosed high-grade osteosarcoma. To determine the overall survival and disease-free survival of these patients. To evaluate the toxicity of this regimen. To correlate MRI imaging of the primary tumor with histopathologic grading after treatment with this regimen. OUTLINE: This is a multicenter study. Neoadjuvant chemotherapy (weeks 1-15): Patients receive ifosfamide IV over 1 hour on days 1-5 and 36-40; doxorubicin hydrochloride IV over 18 hours on days 1-3 and 36-38 and IV over 72 hours on days 71-73; high-dose methotrexate IV over 4 hours on days 22, 29, 57, 64, 92, and 99; and cisplatin IV over 4 hours on day 71. Surgery (week 16): Patients undergo resection of the tumor on day 106. Patients found to have unresectable disease are treated on an alternative protocol unless they have clear clinical and pathologic response to treatment. Adjuvant chemotherapy (weeks 18-43): Beginning 2 weeks after surgery, patients receive ifosfamide IV over 1 hour on days 120-124, 155-159, 225-229, and 260-264; doxorubicin hydrochloride IV over 18 hours on days 120-122 and 155-157 and IV over 72 hours on days 190-192; high-dose methotrexate IV over 4 hours on days 141, 148, 176, 183, 211, 218, 246, 253, 281, and 288; and cisplatin IV over 4 hours on days 190 and 289. After completion of study therapy, patients are followed every 2 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Official Title
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Treatment of Newly Diagnosed Untreated Osteosarcoma: A Pilot Study of a New Chemotherapeutic Regimen Including Ifosfamide

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: ifosfamide
* Drug: methotrexate
* Procedure: adjuvant therapy
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed osteosarcoma of the extremity High-grade (grade III or IV) disease No low-grade disease (e.g., parosteal or periosteal osteosarcoma) No secondary osteosarcoma (i.e., tumor occurring in a radiotherapy field designed for a prior tumor) No Paget's disease No known metastases PATIENT CHARACTERISTICS: Total bilirubin < 2 times normal AST < 2 times normal Alkaline phosphatase < 2 times normal Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min LVEF ≥ 45% Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior malignancy except retinoblastoma Patients with familial retinoblastoma syndrome who develop osteosarcoma unrelated to radiotherapy (e.g., in a primary site in the extremities) are eligible PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy Patients with retinoblastoma may have received radiotherapy to the orbits At least 28 days since prior initial amputation
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: ifosfamide|nan|
|Drug: methotrexate|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: therapeutic conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathologic response rate |  |  | 
| Clinical response rate |  |  | 
| Toxicity |  |  | 
| Disease-free survival |  |  | 
| Overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized osteosarcoma