Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma
Condition: Localized Osteosarcoma; Metastatic Osteosarcoma
MeSH terms: Osteosarcoma
Intervention: Cisplatin; Doxorubicin Hydrochloride; Etoposide; Ifosfamide; Methotrexate; Peginterferon Alfa-2b; Quality-of-Life Assessment; Questionnaire Administration; Therapeutic Conventional Surgery
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given subcutaneously; Ancillary studies; Ancillary studies; Undergo amputation or limb salvage surgery
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b; Interferon-alfa-1b; Cisplatin; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Podophyllotoxin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1334.0
Sex: All
Minimum age: 5 Years
Maximum age: 40 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying combination chemotherapy followed by surgery and
      two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to
      compare how well they work in treating patients with osteosarcoma. 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. Biological therapies, such as PEG-interferon alfa-2b, may interfere with
      the growth of tumor cells. Giving combination chemotherapy before surgery may shrink the
      tumor so it can be removed. Giving combination chemotherapy together with PEG-interferon
      alfa-2b after surgery may kill any remaining tumor cells. It is not yet known whether giving
      combination therapy together with PEG-interferon alfa-2b is more effective than two different
      combination chemotherapy regimens alone after surgery in treating osteosarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed high-grade osteosarcoma, including second malignancies

               -  Localized or metastatic disease

               -  The primary tumor must be located in the limbs or axial skeleton, including any
                  of the following sites*:

                    -  Long bone of upper limb

                    -  Short bone of upper limb

                    -  Long bone of lower limb

                    -  Short bone of lower limb

                    -  Vertebral column

                    -  Ribs, sternum, clavicle, or scapula

                    -  Pelvic bones, sacrum, or coccyx

          -  Tumor (primary, metastatic, or both) resectable OR is expected to become resectable
             after neoadjuvant induction chemotherapy

          -  Suitable for neoadjuvant chemotherapy

          -  Performance status - Lansky 50-100% (for patients under 16 years of age)

          -  Performance status - Karnofsky 50-100%*

          -  Performance status - WHO or ECOG 0-2*

          -  Platelet count ≥ 100,000/mm³

          -  Neutrophil count ≥ 1,500/mm³

          -  WBC ≥ 3,000/mm³

          -  Bilirubin ≤ 1.5 times upper limit of normal

          -  Creatinine clearance ≥ 70 mL/min

          -  Creatinine based on age as follows:

               -  No greater than 1.0 mg/dL (for patients 5 to 10 years of age)

               -  No greater than 1.2 mg/dL (for patients 11 to 15 years of age)

               -  No greater than 1.5 mg/dL (for patients over 15 years of age)

          -  Ejection fraction ≥ 50% by radionuclide angiogram

          -  Shortening fraction ≥ 28% by echocardiogram

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No known HIV positivity

          -  No prior chemotherapy for any disease

          -  Prior radiotherapy for another malignancy allowed

          -  No prior treatment for osteosarcoma

          -  No patients with any of the following:

               -  Craniofacial osteosarcoma