Text Size

Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

This study is currently recruiting participants.
Verified June 2013 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01231906
First received: October 29, 2010
Last updated: June 10, 2013
Last verified: June 2013
History of Changes
  Purpose

This randomized phase III trial is studying combination chemotherapy in treating patients with non-metastatic extracranial Ewing sarcoma. 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.


Condition Intervention Phase
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
 Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Drug: cyclophosphamide
Drug: ifosfamide
Drug: etoposide
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: Time from study enrollment to disease progression, appearance of disease at sites considered previously uninvolved, diagnosis of a second malignant neoplasm, death or last patient contact, assessed up to 10 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Time from study enrollment to death or last patient contact, assessed up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relative risk for death [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the stratified partial likelihood for the relative risk regression model accounting for the factors used to stratify randomization at the time full information is obtained for the event-free survival (EFS) comparison. Methods for censored survival data, including but not limited to log-rank comparisons and proportional hazards regression modeling will be used to assess prognostic significance.

  • Histological response, in terms of event free survival after local control in patients who received local control therapy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Methods for censored survival data, including but not limited to log-rank comparisons and proportional hazards regression modeling will be used.

  • Positron emission tomography (PET)-determined response, in terms of event free survival after local control [ Time Frame: Up to week 13 ] [ Designated as safety issue: No ]
    Methods for censored survival data, including but not limited to log-rank comparisons and proportional hazards regression modeling will be used.

  • Probabilities of identifying tumors of at least 200 ml [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    A two sided log-rank test of size 0.05 as a function of the percent of patients for whom measurements can be obtained will be used.

  • Extent of tumor necrosis according to the necrosis grading criteria in patients who have surgical resection of tumor [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
    The probabilities of identifying patients with 'standard' necrosis grading as associated with increased risk using a two sided log-rank test of size 0.05 as a function of the percent of patients with 'standard' necrosis grading and its associated relative risk will be used.

  • Radiological response of soft tissue component of mass by PET [ Time Frame: Up to week 13 ] [ Designated as safety issue: No ]
    The probabilities of identifying patients with complete response (CR) as associated with decreased risk for EFS-event when compared with patients with less-than-CR using a two sided log-rank test of size 0.05 as a function of the percent of patients with standard response and its associated relative risk will be used.

  • Differences associated with local control modality on risk for EFS event, according to surgery only v. radiation therapy only v. surgery and radiation therapy [ Time Frame: Up to week 13 ] [ Designated as safety issue: No ]
    Stratified according to primary site of tumor as pelvis v. bone but not pelvis v. extra-osseous site. An omnibus log-rank test of size 0.05 will be used to assess whether there are differences associated with local control modality.

  • Number and proportion of patients who experience any grade 2 or higher musculoskeletal event (ME), or surgery required to treat a complication of local therapy based on the NCI CTCAE v4.0 [ Time Frame: Up to 3 months post-local control therapy ] [ Designated as safety issue: Yes ]
    The proportion of patients who experience any ME will be compared across the three regimens using an exact test of proportions of size 0.05.

  • Proportion of patients who have tumor present at the margin of resection on risk for EFS event in patients undergoing surgery [ Time Frame: Week 13 ] [ Designated as safety issue: No ]

Estimated Enrollment: 630
Study Start Date: November 2010
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (combination chemotherapy)
Patients receive induction therapy comprising vincristine sulfate 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. Patients then receive consolidation therapy comprising vincristine sulfate 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.
 Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (combination chemotherapy, topotecan hydrochloride)
Patients receive induction therapy comprising 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. Patients then receive consolidation therapy comprising 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.
 Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed extracranial, non-metastatic Ewing sarcoma or primitive neuroectodermal tumors of bone or soft tissue

    • For the purpose of this study, any of the following are considered localized disease:

      • Chest wall tumors with ipsilateral pleural effusions
      • Ipsilateral positive pleural fluid cytology
      • Ipsilateral pleural-based secondary tumor nodules
    • Regional node involvement, based on clinical suspicion confirmed by pathologic documentation, are considered to be non-metastatic disease
    • Tumors arising in the bony skull (extra-dural) are considered to be extracranial

  • No evidence of metastatic disease, including the following:

    • Lesions that are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor
    • Contralateral pleural effusion and contralateral pleural nodules
    • Distant lymph node involvement

    • Pulmonary nodules that meet the following criteria:

      • Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied and negative for Ewing sarcoma
      • Biopsies of solitary nodule < 0.5 cm or multiple nodules < 3.0 cm (are not required but if performed) positive for metastatic disease
  • No tumors arising in the intra-dural soft tissue

  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:

    • 0.4 mg/dL (1 month to < 6 months of age)
    • 0.5 mg/dL (6 months to < 1 year of age)
    • 0.6 mg/dL (1 year to < 2 years of age)
    • 0.8 mg/dL (2 years to < 6 years of age)
    • 1.0 mg/dL (6 years to < 10 years of age)
    • 1.2 mg/dL (10 years to < 13 years of age)
    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST or ALT < 2.5 times ULN
  • Shortening fraction of ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for the duration of study treatment
  • No prior chemotherapy or radiotherapy

  • Prior biopsy of the primary tumor without an attempt at complete or partial resection allowed

    • Patients are still allowed if unplanned excision was attempted or accomplished as long as adequate imaging was obtained prior to surgery
  • No other concurrent chemotherapy or immunomodulating agents (including steroids unless used as an antiemetic)
  • No concurrent sargramostim (GM-CSF)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01231906

  Show 199 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mason Bond Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01231906     History of Changes
Other Study ID Numbers: AEWS1031, NCI-2011-02611, COG-AEWS1031, CDR0000687639, U10CA098543
Study First Received: October 29, 2010
Last Updated: June 10, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Sarcoma, Ewing's
Kidney Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Osteosarcoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Kidney Diseases
Urologic Diseases
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
 Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Doxorubicin
Etoposide
Vincristine
Topotecan
Immunosuppressive Agents

ClinicalTrials.gov processed this record on June 18, 2013