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New Therapeutic Strategies for Patients With Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma

Primary Purpose

Ewing's Sarcoma, Neuroblastoma, Rhabdomyosarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ADR-529
Topotecan
G-CSF
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing's Sarcoma focused on measuring Peripheral Stem Cell Transfusion, Up-Front Phase II Window, Dose-Intensive Vincristine, Dose-Intensive Doxorubicin, Dose-Intensive Cyclophosphamide, ADR-529 for Cardioprotection, BID Radiation Therapy for Local Control

Eligibility Criteria

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

The patient must fall into one of the following diagnostic categories: Ewing's sarcoma family of tumors (ESF): Includes Ewing's sarcoma (classic, atypical, extra-osseous), primitive sarcoma of bone, ectomesenchymoma, or peripheral primitive neuroectodermal tumor (peripheral neuroepithelioma). Rhabdomyosarcoma: The patient must have either High-risk arm: Metastatic disease at diagnosis (any site, any histology); OR Moderate-risk arm: Incompletely resected ( Clinical Group III) Stage II tumors and ALL stage III tumors (regardless of degree of surgical resection). Neuroblastoma: Any patient with metastatic disease at diagnosis (POG stage D or Evans' stage IV); or, patients with loco-regional metastatic disease (POG stage C) or tumor infiltrating across the midline (Evans' stage III) IF they have an elevated serum ferritin (greater than 142 ng/ml), an amplified N-myc copy number (greater than 10 copies on Southern analysis), or a DNA index of greater than 1.1. The patient must not have been previously treated with chemotherapy or radiation therapy. Patients must be greater than or equal to 1 year of age but less than or equal to 25 years of age. Patients weight must be greater than or equal to 15 kg. The patient (or his/her guardian if less than 18 years of age) must sign a document indicating that he/she is aware of the investigational nature of this treatment protocol and the potential risks and benefits that may be expected. Potentially fertile female patients must have a documented negative urine or serum pregnancy test. Patients must have a documented negative HIV serologic evaluation (Western Blot and/or ELISA). Patients must not have abnormal cardiac function (left ventricular ejection fraction less than 45% as measured by gated equilibrium radionuclide angiography [MUGA scan] and confirmed by echocardiography). Patients must not have impaired renal function (serum creatinine greater than or equal to twice the upper limit of normal for age). Patients with a total bilirubin of greater than 4.0 mg/dl (or a direct bilirubin of greater than 2.0 mg/dl) or SGOT/SGPT greater than five times the upper limits of normal (NOT on the basis of hepatic involvement by tumor) will be excluded. Patients with a second malignancy following previous therapy will be excluded. Patients previously treated with chemotherapy or radiation therapy (other than limited, emergency radiation therapy) will be excluded. Patients who are HIV-infected will be excluced.

Sites / Locations

  • National Cancer Institute (NCI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001335
Brief Title
New Therapeutic Strategies for Patients With Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma
Official Title
New Therapeutic Strategies for Patients With Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2002
Overall Recruitment Status
Completed
Study Start Date
April 1993 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2002 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
The prognosis for patients with metastatic Ewing's sarcoma family of tumors (ESF), rhabdomyosarcoma (RMS), and neuroblastoma (NBL) remains dismal, with less than 25% long-term disease-free survival. Though less grave, the prognosis for cure for other high-risk patients is approximately 50%. New treatment strategies, including the identification of highly active new agents, maximizing the dose intensity of the most active standard drugs, and the development of improved methods of consolidation to eradicate microscopic residual disease, are clearly needed to improve the outcome of these patients. This protocol will address these issues by commencing with a Phase II window, for the highest risk patients, to evaluate a series of promising drugs with novel mechanisms of action. All patients will then receive 5 cycles of dose-intensive "best standard therapy" with doxorubicin (adriamycin), vincristine, and cyclophosphamide (VAdriaC). Patients at high risk of relapse will continue onto a phase I consolidation regimen consisting of three cycles of dose-escalated Melphalan, Ifosfamide, Mesna, and Etoposide (MIME). Peripheral blood stem cell transfusions (PBSCT) and recombinant human G-CSF will be used as supportive care measures to allow maximal dose-escalation of this combination regimen.
Detailed Description
The prognosis for patients with metastatic Ewing's sarcoma family of tumors (ESF), rhabdomyosarcoma (RMS), and neuroblastoma (NBL) remains dismal, with less than 25% long-term disease-free survival. Though less grave, the prognosis for cure for other high-risk patients is approximately 50%. New treatment strategies, including the identification of highly active new agents, maximizing the dose intensity of the most active standard drugs, and the development of improved methods of consolidation to eradicate microscopic residual disease, are clearly needed to improve the outcome of these patients. This protocol will address these issues by commencing with a Phase II window, for the highest risk patients, to evaluate a series of promising drugs with novel mechanisms of action. All patients will then receive 5 cycles of dose-intensive "best standard therapy" with doxorubicin (adriamycin), vincristine, and cyclophosphamide (VAdriaC). Patients at high risk of relapse will continue onto a phase I consolidation regimen consisting of three cycles of dose-escalated Melphalan, Ifosfamide, Mesna, and Etoposide (MIME). Peripheral blood stem cell transfusions (PBSCT) and recombinant human G-CSF will be used as supportive care measures to allow maximal dose-escalation of this combination regimen.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing's Sarcoma, Neuroblastoma, Rhabdomyosarcoma
Keywords
Peripheral Stem Cell Transfusion, Up-Front Phase II Window, Dose-Intensive Vincristine, Dose-Intensive Doxorubicin, Dose-Intensive Cyclophosphamide, ADR-529 for Cardioprotection, BID Radiation Therapy for Local Control

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
90 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
ADR-529
Intervention Type
Drug
Intervention Name(s)
Topotecan
Intervention Type
Drug
Intervention Name(s)
G-CSF

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
The patient must fall into one of the following diagnostic categories: Ewing's sarcoma family of tumors (ESF): Includes Ewing's sarcoma (classic, atypical, extra-osseous), primitive sarcoma of bone, ectomesenchymoma, or peripheral primitive neuroectodermal tumor (peripheral neuroepithelioma). Rhabdomyosarcoma: The patient must have either High-risk arm: Metastatic disease at diagnosis (any site, any histology); OR Moderate-risk arm: Incompletely resected ( Clinical Group III) Stage II tumors and ALL stage III tumors (regardless of degree of surgical resection). Neuroblastoma: Any patient with metastatic disease at diagnosis (POG stage D or Evans' stage IV); or, patients with loco-regional metastatic disease (POG stage C) or tumor infiltrating across the midline (Evans' stage III) IF they have an elevated serum ferritin (greater than 142 ng/ml), an amplified N-myc copy number (greater than 10 copies on Southern analysis), or a DNA index of greater than 1.1. The patient must not have been previously treated with chemotherapy or radiation therapy. Patients must be greater than or equal to 1 year of age but less than or equal to 25 years of age. Patients weight must be greater than or equal to 15 kg. The patient (or his/her guardian if less than 18 years of age) must sign a document indicating that he/she is aware of the investigational nature of this treatment protocol and the potential risks and benefits that may be expected. Potentially fertile female patients must have a documented negative urine or serum pregnancy test. Patients must have a documented negative HIV serologic evaluation (Western Blot and/or ELISA). Patients must not have abnormal cardiac function (left ventricular ejection fraction less than 45% as measured by gated equilibrium radionuclide angiography [MUGA scan] and confirmed by echocardiography). Patients must not have impaired renal function (serum creatinine greater than or equal to twice the upper limit of normal for age). Patients with a total bilirubin of greater than 4.0 mg/dl (or a direct bilirubin of greater than 2.0 mg/dl) or SGOT/SGPT greater than five times the upper limits of normal (NOT on the basis of hepatic involvement by tumor) will be excluded. Patients with a second malignancy following previous therapy will be excluded. Patients previously treated with chemotherapy or radiation therapy (other than limited, emergency radiation therapy) will be excluded. Patients who are HIV-infected will be excluced.
Facility Information:
Facility Name
National Cancer Institute (NCI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Learn more about this trial

New Therapeutic Strategies for Patients With Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma

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