Trial record 1 of 1 for:    AEWS1031
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Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01231906
First received: October 29, 2010
Last updated: February 5, 2014
Last verified: February 2014

October 29, 2010
February 5, 2014
November 2010
September 2019   (final data collection date for primary outcome measure)
  • 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 ]
  • Event-free survival (EFS) [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01231906 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Histologic response [ Designated as safety issue: No ]
  • Initial volumetric tumor size as a prognostic factor for EFS [ Designated as safety issue: No ]
  • Prognostic significance of imaging response by FDG-positron emission tomography (PET) and EFS [ Designated as safety issue: No ]
  • Effect of local surgical margins in conjunction with histologic response on EFS [ Designated as safety issue: No ]
  • Effect of local therapy modality (surgery, radiotherapy or a combination) as well as the type of surgical reconstruction on musculoskeletal complications [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma
A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma

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.

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To evaluate initial volumetric tumor size as a prognostic factor for 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 FDG-positron emission tomography (PET) as a prognostic factor for EFS.

V. 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: This is a multicenter study. Patients are stratified according to age (≤ 17 years vs ≥ 18 years) and primary tumor site (pelvic vs non-pelvic vs extra-osseous). Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION THERAPY: Patients receive 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.

CONSOLIDATION THERAPY: Patients receive 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.

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 periodically for 10 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
  • 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.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: ifosfamide
    • Drug: etoposide
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: ifosfamide
    • Drug: etoposide
    • Drug: topotecan hydrochloride
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
630
Not Provided
September 2019   (final data collection date for primary outcome measure)

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)
Both
up to 50 Years
No
United States,   Australia,   Canada,   New Zealand
 
NCT01231906
AEWS1031, NCI-2011-02611, COG-AEWS1031, CDR0000687639, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Mason Bond Children's Oncology Group
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP