Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma
Condition: Localized Extraskeletal Ewing Sarcoma; Peripheral Primitive Neuroectodermal Tumor of Bone; Peripheral Primitive Neuroectodermal Tumor of Soft Tissues
MeSH terms: Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Soft Tissue Neoplasms
Intervention: Cyclophosphamide; Dexrazoxane; Doxorubicin Hydrochloride; Etoposide; Ifosfamide; Laboratory Biomarker Analysis; Topotecan Hydrochloride; Vincristine Sulfate
Intervention description: Given IV; Given IV; Given IV; Given IV; Correlative studies; Given IV; Given IV
Intervention MeSH terms: Cyclophosphamide; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Etoposide phosphate; Topotecan; Podophyllotoxin; Dexrazoxane; Razoxane; 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 642.0
Sex: All
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      This trial examined the outcome benefit to patients of adding a new chemotherapy drug
      combination to the established treatment approach for patients with extracranial Ewing
      sarcoma, that had not spread from the primary site to other places in the body. The trial
      randomly assigned patients at the time of study entry to receive established standard
      treatment with the following 5-drugs: vincristine sulfate, doxorubicin hydrochloride,
      cyclophosphamide, ifosfamide and etoposide. The outcome for patients receiving the standard
      5-drug combination was compared to the outcome for patients who received the same 5-drugs
      with an additional drug, topotecan hydrochloride delivered in a novel combination with
      vincristine sulfate and cyclophosphamide.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing
             sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue are eligible
             for this study; note:

               -  For the purpose of this study, chest wall tumors with ipsilateral pleural
                  effusions, ipsilateral positive pleural fluid cytology or ipsilateral pleural
                  based secondary tumor nodules will be considered localized disease

               -  Patients with regional node involvement, based on clinical suspicion confirmed by
                  pathologic documentation are considered to be non-metastatic

               -  Patients with discontinuous osseous lesions within the same bone are considered
                  to be non-metastatic

               -  Tumors arising in the bony skull (extra-dural) are considered to be extracranial

          -  Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by
             institutional pathologist

          -  No prior chemotherapy or radiation therapy is allowed; patients should only have had a
             biopsy of the primary tumor without an attempt at complete or partial resection;
             patients will still be eligible if unplanned excision was attempted or accomplished as
             long as adequate imaging was obtained prior to surgery

          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73
             m^2 or serum creatinine based on age/gender as follows:

               -  1 month to < 6 months: 0.4 mg/dL

               -  6 months to < 1 year: 0.5 mg/dL

               -  1 to < 2 years: 0.6 mg/dL

               -  2 to < 6 years: 0.8 mg/dL

               -  6 to < 10 years: 1 mg/dL

               -  10 to < 13 years: 1.2 mg/dL

               -  13 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)

               -  >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)

          -  Total bilirubin < 1.5 x upper limit of normal (ULN) for age

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
             upper limit of normal (ULN) for age

          -  Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
             radionuclide angiogram

        Exclusion Criteria:

          -  Patients must have no evidence of metastatic disease; metastatic disease are lesions
             which are discontinuous from the primary tumor, are not regional lymph nodes and do
             not share a body cavity with the primary tumor; if there is any doubt whether lesions
             are metastatic, a biopsy of those lesions should be taken

               -  Skeletal lesions in adjacent bones (trans-articular)

               -  Contralateral pleural effusion and contralateral pleural nodules

               -  Distant lymph node involvement

               -  Patients with pulmonary nodules are considered to have metastatic disease if the
                  patient has:

                    -  Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied and
                       negative for Ewing's

                    -  Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not
                       required but if performed and positive indicate metastatic disease

          -  Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium
             and spine are not eligible

          -  Patients with pathologic diagnoses other than Ewing sarcoma will be excluded

          -  Patients diagnosed with Ewing Sarcoma as a second malignant neoplasm are not eligible
             if they have received chemotherapy or radiation for the treatment of their primary
             malignancy

          -  Pregnant women will not be entered on this study; pregnancy tests must be obtained in
             female patients who are post-menarchal; lactating females may not participate unless
             they have agreed not to breastfeed their infants; males or females of reproductive
             potential may not participate unless they have agreed to use an effective
             contraceptive method for the duration of the study treatment

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met