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| Sponsored by: |
National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00001335 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Ewing's Sarcoma Neuroblastoma Rhabdomyosarcoma |
Drug: ADR-529 Drug: Topotecan Drug: G-CSF |
Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Safety/Efficacy Study |
| Official Title: | New Therapeutic Strategies for Patients With Ewing's Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma |
| Estimated Enrollment: | 90 |
| Study Start Date: | April 1993 |
| Estimated Study Completion Date: | January 2002 |
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.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations More Information
| Study ID Numbers: | 930125, 93-C-0125 |
| Study First Received: | November 3, 1999 |
| Last Updated: | March 3, 2008 |
| ClinicalTrials.gov Identifier: | NCT00001335 |
| Health Authority: | United States: Federal Government |
|
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 |
|
Neuroectodermal Tumors, Primitive Ewing's family of tumors Malignant mesenchymal tumor Vincristine Osteosarcoma Cyclophosphamide Osteogenic sarcoma Doxorubicin Neuroblastoma Soft tissue sarcomas Razoxane |
Neuroectodermal Tumors Neoplasms, Connective and Soft Tissue Ewing's sarcoma Sarcoma, Ewing's Neoplasms, Germ Cell and Embryonal Sarcoma Neuroepithelioma Topotecan Neuroectodermal Tumors, Primitive, Peripheral Rhabdomyosarcoma Neoplasms, Glandular and Epithelial |
|
Neoplasms, Muscle Tissue Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myosarcoma Neoplasms, Nerve Tissue Cardiovascular Agents |
Pharmacologic Actions Neoplasms Neoplasms, Bone Tissue Therapeutic Uses Neoplasms, Connective Tissue Chelating Agents Neoplasms, Neuroepithelial |
