Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma
Condition: Sarcoma
MeSH terms: Osteosarcoma
Intervention: cisplatin; dexrazoxane hydrochloride; doxorubicin hydrochloride; etoposide; ifosfamide; leucovorin calcium; methotrexate; zoledronic acid; adjuvant therapy; neoadjuvant therapy; therapeutic conventional surgery; filgrastim; Mesna
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given IV or orally; Given IV; Given IV; Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.; Given SC; Given IV
Intervention MeSH terms: Zoledronic Acid; Leucovorin; Cisplatin; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Ifosfamide; Isophosphamide mustard; Dexrazoxane; Razoxane; Imidazole; Lenograstim; Levoleucovorin; Mesna
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Maximum age: 40 Years
Healthy volunteers: No
Keywords: metastatic osteosarcoma

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Giving more than one
      drug (combination chemotherapy) may kill more tumor cells.

      PURPOSE: This clinical trial is studying the side effects and best dose of zoledronic acid
      when given together with combination chemotherapy in treating patients with newly diagnosed
      metastatic osteosarcoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Biopsy-proven high-grade osteosarcoma within the past 6 weeks

               -  Newly diagnosed disease

               -  Metastatic disease

          -  Resectable disease OR expected to become resectable after initial chemotherapy

          -  Disease has arisen outside of areas of Paget's disease

        PATIENT CHARACTERISTICS:

          -  ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (for patients > 16 years of
             age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)

          -  Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR maximum
             serum creatinine based on age/gender as follows:

               -  0.4 mg/dL (for patients 1 to 5 months of age)

               -  0.5 mg/dL (for patients 6 to 11 months of age)

               -  0.6 mg/dL (for patients 1 year of age)

               -  0.8 mg/dL (for patients 2 to 5 years of age)

               -  1 mg/dL (for patients 6 to 9 years of age)

               -  1.2 mg/dL (for patients 10 to 12 years of age)

               -  1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

               -  1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

          -  AST or ALT < 2.5 times ULN for age

          -  Shortening fraction ≥ 28% by echocardiogram OR ejection fraction ≥ 50% by radionuclide
             angiogram

          -  ANC ≥ 1,000/mm³

          -  Platelet count ≥ 100,000/mm³ (transfusion independent)

          -  Hemoglobin ≥ 10 g/dL (RBC transfusion allowed)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use contraception

          -  No known HIV infection

          -  No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction
             disturbances

        PRIOR CONCURRENT THERAPY:

          -  No prior chemotherapy or radiotherapy

          -  No other concurrent anticancer chemotherapy

          -  No concurrent immunomodulating agents

          -  Steroids for anti-emetic allowed