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Two Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors

Primary Purpose

Ewing Sarcoma of Bone, Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
radiation therapy
therapeutic conventional surgery
etoposide
ifosfamide
doxorubicin hydrochloride
cyclophosphamide
vincristine sulfate
topotecan hydrochloride
filgrastim
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing Sarcoma of Bone

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of extracranial Ewing sarcoma or peripheral primitive neuroectodermal tumor of bone or soft tissue:

    • Newly diagnosed disease
    • Disease confirmed by biopsy only with no attempt at complete or partial resection

      • Unplanned excision allowed provided adequate imaging was obtained prior to surgery and incompletely resected disease is controlled by local therapy
    • No esthesioneuroblastoma
  • Localized disease, including any of the following sites:

    • Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural based secondary tumor nodules;

      • No contralateral pleural effusions or pleural nodules
    • Regional lymph nodes that are clinically suspicious or confirmed by biopsy

      • No distant lymph node metastases
    • Extra-dural tumors arising in the bony skull

      • No tumors arising in the intra-dural soft tissue or the intra-dural region of the spine
  • No evidence of metastatic disease, defined as any of the following:

    • Lesions that are discontinuous from the primary tumor
    • Lesions that are not regional lymph nodes
    • Lesions that do not share a body cavity with the primary tumor
  • No evidence by CT scan of metastatic lung disease, defined as any of the following:

    • One pulmonary nodule > 1 cm in diameter or more than one nodule > 0.5 cm diameter

      • Pulmonary nodules that are resected and are not found to be metastatic Ewing sarcoma are allowed
    • Biopsy proven solitary nodules measuring 0.5 to 1.0 cm or multiple nodules measuring 0.3 to 0.5 cm

      • Solitary nodules measuring < 0.5 cm or multiple nodules measuring < 0.3 cm are allowed unless biopsy proven to be metastatic (biopsy is not required)
  • Karnofsky performance status (PS) 0-2 (>= 16 years old) OR Lansky PS 0-2 (< 16 years old)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age/gender as follows:

    • 1 month to < 6 months old (males and females 0.4 mg/dL)
    • 6 months to < 1 year old (males and females 0.5 mg/dL)
    • 1 to < 2 years old (males and females 0.6 mg/dL)
    • 2 to < 6 years old (males and females 0.8 mg/dL)
    • 6 to < 10 years old (males and females 1.0 mg/dL)
    • 10 to < 13 years old (males and females 1.2 mg/dL)
    • 13 to < 16 years old (males 1.5 mg/dL and females 1.4 mg/dL)
    • >= 16 years old (males 1.7 mg/dL and females 1.4 mg/dL)
  • AST or ALT < 2.5 times ULN for age
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
  • Shortening fraction of >= 27% by ECHO or ejection fraction of >= 50% by radionuclide angiogram (MUGA)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior chemotherapy or radiotherapy
  • No concurrent pegfilgrastim (Neulasta) or sargramostim (GM-CSF)
  • No other concurrent cancer chemotherapy or immunomodulating agents, including steroids, unless used as an antiemetic

Sites / Locations

  • Children's Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (combination chemotherapy)

Arm Description

See Detailed Description

Outcomes

Primary Outcome Measures

Incidence of Death
Incidence of death from complications of therapy while the patient is on protocol therapy or within one month of terminating protocol therapy
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Enrollment to Week 12
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Week 13 to Week 22
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Week 23 to Week 28
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Week 29 to Week 37
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.

Secondary Outcome Measures

Event Free Survival
Disease progression, occurrence of a second malignant neoplasm (SMN)or death will be considered an analytic event. In all other cases, the patient will be considered censored at last contact.

Full Information

First Posted
February 19, 2008
Last Updated
September 11, 2014
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00618813
Brief Title
Two Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors
Official Title
A Pilot Study of Chemotherapy Intensification by Adding Vincristine, Topotecan and Cyclophosphamide to Standard Chemotherapy Agents With an Interval Compression Schedule in Newly Diagnosed Patients With Localized Ewing Sarcoma Family of Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This clinical trial is studying the side effects of combination chemotherapy and to see how well they work in treating patients with newly diagnosed localized Ewing sarcoma family of tumors. 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) and giving the drugs in different ways may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the feasibility and safety of adding interval-compressed vincristine, topotecan hydrochloride, and cyclophosphamide to a treatment protocol utilizing interval compression of vincristine, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide in patients with localized Ewing sarcoma family of tumors. SECONDARY OBJECTIVES: I. To estimate the event-free survival in patients treated with this regimen. OUTLINE: This is a multicenter study. INDUCTION THERAPY (WEEKS 1-12): Patients receive vincristine 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 1 hour on days 1-5 in weeks 1 and 9 and on day 1 in weeks 5 and 11; ifosfamide IV over 1 hour on days 1-5 in weeks 3 and 7; etoposide IV over 1 hour on days 1-5 in weeks 3 and 7; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 5 and 11. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning 24-36 hours after the last dose of chemotherapy and continuing for at least 7 days or until blood counts recover, whichever comes last. Filgrastim is discontinued at least 24 hours prior to the next course of chemotherapy. LOCAL CONTROL: Patients who respond to induction therapy may undergo surgery alone if the lesion can be resected with negative margins and with a reasonable functional result beginning in week 13. Following surgery, patients with unresectable lesions or inadequate margins may receive radiotherapy during week 15. Patients with bulky lesions in surgically difficult sites such as the spine, skull, and periacetabular pelvis; poor response to induction chemotherapy; or those in whom surgery would result in unacceptable functional results may receive radiotherapy alone in weeks 13-19. Patients with bulky lesions in difficult sites and who do not have a good clinical and radiographic response to induction therapy may receive radiotherapy to the primary site during weeks 13-19 followed by surgery of the involved site during week 25 after recovery from course 11 of chemotherapy. Patients with microscopic residual disease after planned pre-operative radiotherapy will receive additional radiotherapy. CONTINUATION THERAPY (WEEKS 15-36): Patients receive vincristine IV on day 1 in weeks 15, 16, 21-24, 27-30, 33, and 34; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 15, 21, and 29; cyclophosphamide IV over 1 hour on days 1-5 in weeks 15, 21 and 29 and on day 1 in weeks 23, 27, and 33; ifosfamide IV over 1 hour on days 1-5 in weeks 17, 19, 25, 31, and 35; etoposide IV over 1 hour on days 1-5 in weeks 17, 19, 25, 31, and 35; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 of weeks 23, 27, and 33. Patients also receive G-CSF SC as in induction therapy. After completion of study treatment, patients are followed for 10 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing Sarcoma of Bone, Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (combination chemotherapy)
Arm Type
Experimental
Arm Description
See Detailed Description
Intervention Type
Other
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Other
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Undergo surgery
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Other Intervention Name(s)
Cyfos, Holoxan, IFF, IFX, IPP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
leurocristine sulfate, VCR, Vincasar PFS
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Other Intervention Name(s)
hycamptamine, Hycamtin, SKF S-104864-A, TOPO
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given SC
Primary Outcome Measure Information:
Title
Incidence of Death
Description
Incidence of death from complications of therapy while the patient is on protocol therapy or within one month of terminating protocol therapy
Time Frame
Length of protocol therapy (up to 37 weeks) plus 30 days
Title
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Enrollment to Week 12
Description
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Time Frame
Enrollment to week 12
Title
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Week 13 to Week 22
Description
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Time Frame
Week 13 to week 22
Title
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Week 23 to Week 28
Description
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Time Frame
Week 23 to week 28
Title
Incidence Rate (Number of Participants) of Dose-limiting Toxicity (DLT) - Week 29 to Week 37
Description
The incidence rate of DLT while on protocol therapy where DLT is defined as (1) Grade 3 or greater nonhematological adverse event that is possibly, probably, or likely related to therapy with the specific exception of Grade 3 or greater nausea or vomiting controlled by standard supportive care measures, Grade 3 infection and Grade 3 alopecia; or (2) Grade 4 or higher hematological AE that delays the administration of therapy at least 2 weeks.
Time Frame
Week 29 to week 37
Secondary Outcome Measure Information:
Title
Event Free Survival
Description
Disease progression, occurrence of a second malignant neoplasm (SMN)or death will be considered an analytic event. In all other cases, the patient will be considered censored at last contact.
Time Frame
From enrollment to event or 10 years from enrollment, whichever occurs first

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of extracranial Ewing sarcoma or peripheral primitive neuroectodermal tumor of bone or soft tissue: Newly diagnosed disease Disease confirmed by biopsy only with no attempt at complete or partial resection Unplanned excision allowed provided adequate imaging was obtained prior to surgery and incompletely resected disease is controlled by local therapy No esthesioneuroblastoma Localized disease, including any of the following sites: Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural based secondary tumor nodules; No contralateral pleural effusions or pleural nodules Regional lymph nodes that are clinically suspicious or confirmed by biopsy No distant lymph node metastases Extra-dural tumors arising in the bony skull No tumors arising in the intra-dural soft tissue or the intra-dural region of the spine No evidence of metastatic disease, defined as any of the following: Lesions that are discontinuous from the primary tumor Lesions that are not regional lymph nodes Lesions that do not share a body cavity with the primary tumor No evidence by CT scan of metastatic lung disease, defined as any of the following: One pulmonary nodule > 1 cm in diameter or more than one nodule > 0.5 cm diameter Pulmonary nodules that are resected and are not found to be metastatic Ewing sarcoma are allowed Biopsy proven solitary nodules measuring 0.5 to 1.0 cm or multiple nodules measuring 0.3 to 0.5 cm Solitary nodules measuring < 0.5 cm or multiple nodules measuring < 0.3 cm are allowed unless biopsy proven to be metastatic (biopsy is not required) Karnofsky performance status (PS) 0-2 (>= 16 years old) OR Lansky PS 0-2 (< 16 years old) Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age/gender as follows: 1 month to < 6 months old (males and females 0.4 mg/dL) 6 months to < 1 year old (males and females 0.5 mg/dL) 1 to < 2 years old (males and females 0.6 mg/dL) 2 to < 6 years old (males and females 0.8 mg/dL) 6 to < 10 years old (males and females 1.0 mg/dL) 10 to < 13 years old (males and females 1.2 mg/dL) 13 to < 16 years old (males 1.5 mg/dL and females 1.4 mg/dL) >= 16 years old (males 1.7 mg/dL and females 1.4 mg/dL) AST or ALT < 2.5 times ULN for age Total bilirubin =< 1.5 times upper limit of normal (ULN) for age Shortening fraction of >= 27% by ECHO or ejection fraction of >= 50% by radionuclide angiogram (MUGA) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior chemotherapy or radiotherapy No concurrent pegfilgrastim (Neulasta) or sargramostim (GM-CSF) No other concurrent cancer chemotherapy or immunomodulating agents, including steroids, unless used as an antiemetic
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leo Mascarenhas, MD MS
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Monrovia
State/Province
California
ZIP/Postal Code
91016
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Two Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors

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