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Summary

for people ages up to 50 years (full criteria)
at Oakland, California and other locations
study started
estimated completion:

Description

Summary

This randomized phase III trial studies combination chemotherapy to see how well it works compared to combination chemotherapy with topotecan hydrochloride in treating patients with non-metastatic extracranial Ewing sarcoma. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, etoposide, and topotecan hydrochloride, 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. It is not yet known whether combination chemotherapy is more effective with topotecan hydrochloride in treating Ewing sarcoma.

Official Title

A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma

Details

PRIMARY OBJECTIVES:

  1. Test the effect of the combination of vincristine (vincristine sulfate), cyclophosphamide, and topotecan (topotecan hydrochloride) (VTC) added to the standard 5-drug chemotherapy interval-compressed backbone on event-free and overall survival of children and young adults with Ewing sarcoma.

SECONDARY OBJECTIVES:

  1. To evaluate initial volumetric tumor size as a prognostic factor for event free survival (EFS) in patients with localized Ewing tumors.

II. To evaluate histologic response as a prognostic factor for EFS in patients with localized Ewing tumors.

III. To continue evaluation of biologic markers both as related to prognosis and as eventual therapeutic targets via encouraging concurrent enrollment on a Ewing sarcoma specimen-collection study.

IV. To evaluate imaging response by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) as a prognostic factor for EFS.

  1. To evaluate the effects of the type of local therapy on EFS and overall survival.

VI. To evaluate the effect of local surgical margins in conjunction with histologic response on EFS in patients with localized Ewing tumors.

VII. To evaluate the effect of local therapy modality (surgery, radiotherapy, or a combination) as well as the type of surgical reconstruction on musculoskeletal complications.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) on day 1 in weeks 1, 2, 5, 6, 9, and 10; doxorubicin hydrochloride IV on days 1 and 2 and cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 5, and 9; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 7, and 11.

CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7, 8, 9, 10, 13, 14, 17, 18, 21, and 22; doxorubicin hydrochloride IV on days 1 and 2 in weeks 1 and 9; cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 7, 9, 13, 17, and 21; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 5, 11, 15, and 19.

ARM II:

INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9, 10, 11 and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 9; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1 and 9, and on day 1 of weeks 5 and 11; ifosfamide and etoposide as in arm I; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 5 and 11.

CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7-10, 13-16, 19, and 20; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1, 7, and 15; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1, 7, and 15, and on day 1 in weeks 9, 13, and 19; ifosfamide IV over 1 hour and etoposide IV over 1- 2 hours on days 1-5 in weeks 3, 5, 11, 17, and 21; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 9,13, and 19.

Patients with responsive or stable disease undergo may undergo surgery alone in week 13 if lesion can be complete resected with negative margins and with reasonable functional result. Patients with unresectable lesions or inadequate margins after surgery receive radiotherapy during weeks 1-7. Patients with bulky lesions in surgically difficult sites such as the spine, skull, and periacetabular pelvis, patients with a poor response to induction chemotherapy, or those patients in whom surgery would result in unacceptable functional results may undergo radiotherapy alone in weeks 1-7 of consolidation therapy, and surgery should be performed after completion of consolidation chemotherapy. Patients with microscopic residual disease after planned pre-operative radiotherapy receive additional radiotherapy.

After completion of study therapy, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.

Keywords

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET) Childhood Supratentorial Primitive Neuroectodermal Tumor Ewing Sarcoma of Bone Extraosseous Ewing Sarcoma Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Peripheral Primitive Neuroectodermal Tumor of the Kidney Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor Cyclophosphamide Ifosfamide Isophosphamide mustard Liposomal doxorubicin Etoposide phosphate Doxorubicin Etoposide Vincristine Topotecan

Eligibility

You can join if…

Open to people ages up to 50 years

  • 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 m2 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

You CAN'T join if...

  • 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

Locations

  • Kaiser Permanente-Oakland
    Oakland, California, 94611, United States
  • Children's Hospital Central California
    Madera, California, 93636-8762, United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California, 94304, United States
  • UC Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Children's Hospital Los Angeles
    Los Angeles, California, 90027, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California, 90048, United States
  • City of Hope
    Duarte, California, 91010, United States
  • Southern California Permanente Medical Group
    Downey, California, 90242, United States
  • David Geffen School of Medicine at UCLA
    Los Angeles, California, 90095, United States
  • Mattel Children's Hospital UCLA
    Los Angeles, California, 90095, United States
  • Miller Children's Hospital
    Long Beach, California, 90806, United States
  • Childrens Hospital of Orange County
    Orange, California, 92868-3874, United States
  • University of California Medical Center At Irvine-Orange Campus
    Orange, California, 92868, United States
  • Loma Linda University Medical Center
    Loma Linda, California, 92354, United States
  • Nevada Cancer Research Foundation CCOP
    Las Vegas, Nevada, 89106, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Oncology Group
ID
NCT01231906
Phase
Phase 3
Study Type
Interventional
Last Updated
February 1, 2017