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Combination Chemotherapy, Peripheral Stem Cell Transplantation, and Radiation Therapy in Treating Patients With Ewing's Sarcoma, Peripheral Primitive Neuroectodermal Tumor, or Rhabdomyosarcoma
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003081
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy, peripheral stem cell transplantation, and radiation therapy in treating patients with recurrent metastatic Ewing's sarcoma, peripheral primitive neuroectodermal tumor, or rhabdomyosarcoma.


Condition Intervention Phase
Sarcoma
Drug: busulfan
Drug: filgrastim
Drug: melphalan
Drug: thiotepa
Procedure: peripheral blood stem cell transplantation
Procedure: radiation therapy
Phase I

MedlinePlus related topics: Cancer Soft Tissue Sarcoma
Drug Information available for: Filgrastim Melphalan Thiotepa Melphalan hydrochloride Sarcolysin Busulfan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Trial of Busulfan, Thiotepa and Melphalan Followed by Autologous or Syngeneic Peripheral Blood Stem Cell Transplantation and Followed by Total Marrow (Skeletal) Irradiation (TMI) in Patients With High-Risk Ewing's Sarcoma, PNET or Rhabdomyosarcoma

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 16
Study Start Date: March 1998
Detailed Description:

OBJECTIVES: I. Estimate the maximum tolerated dose of total bone marrow irradiation (TMI) that can be administered as planned consolidation utilizing autologous peripheral blood stem cell support following local radiotherapy (if indicated) and prior busulfan, melphalan, and thiotepa. II. Examine the efficacy of this dual transplant approach for high-risk patients with Ewing's sarcoma, peripheral primitive neuroectodermal tumor, or rhabdomyosarcoma in first complete remission or greater.

OUTLINE: This is a two part, radiation dose escalation study. Peripheral blood stem cells (PBSC) are collected after 5-6 daily injections of G-CSF. The PBSC are infused in two halves. One half is given after chemotherapy and the other half after total marrow irradiation (TMI). Transplant #1 (part one) consists of chemotherapy and PBSC infusion. Busulfan (BU) is administered orally every 6 hours for 3 days for a total of 12 doses on days -8, -7 and -6. Melphalan is intravenously infused over 30 minutes for 2 days on days -5 and -4. Thiotepa is intravenously infused over 2 hours on days -3 and -2. PBSC are infused on day 0, 36-48 hours after completion of chemotherapy. Patients are considered for local irradiation therapy between transplant #1 and #2 if tissue limiting irradiation doses to bulk tumor site have not previously been administered. The local irradiation is given immediately prior to TMI administration. Transplant #2 starts sometime between day 60 and 120 after transplant #1. For transplant #2, cohorts of 4 patients are treated with TMI twice a day for 5 days at initial dose level on days -5 through -1. TMI is administered over 30-40 minutes. The second half of the PBSC is infused 1-24 hours following the last dose of TMI. After treatment of at least 4 patients at the initial TMI dose level, dose levels escalate in the absence of toxicity. If there is no dose limiting toxicity (DLT) in the current group of 4 patients, the next cohort is treated at the next higher dose level. If 1 of the 4 patients experiences DLT, the next cohort is treated at the same dose. If 1 DLT is seen among 8 patients treated at a dose, then the next cohort is treated at the next higher dose level. If 2 patients out of 8 experience DLT, this dose is identified as the maximum tolerated dose (MTD). If 1 out of 4 or 3 out 8 patients experience DLT at a dose level, the next lower dose level is identified as the MTD. Each patient in a cohort is observed for a minimum of 28 days prior to escalation to the higher dose level. Tumor restaging occurs approximately 9 months after initial transplant, then at 12 months and annually thereafter.

PROJECTED ACCRUAL: An expected 12-16 patients are required to complete this study. Accrual should last 3-4 years at 4-5 patients per year.

  Eligibility

Ages Eligible for Study:   up to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically confirmed recurrent metastatic Ewing's sarcoma, peripheral primitive neuroectodermal tumor (PNET) or Clinical Group IV rhabdomyosarcoma Complete remission or very good partial remission (at least 50% reduction in measurable tumor burden) following initial chemotherapy with or without surgery No primary CNS PNET

PATIENT CHARACTERISTICS: Age: Under 50 Performance status: Karnofsky 70-100% Life expectancy: Greater than 3 months Hematopoietic: Granulocyte count at least 1,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 2.0 mg/dL Renal: Creatinine clearance greater than 50% of normal Pulmonary: LVEF greater than 41% Other: HIV negative Not pregnant

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: No prior dose limiting irradiation to any organ site Surgery: See Disease Characteristics

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003081

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Jean E. Sanders, MD Fred Hutchinson Cancer Research Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Study ID Numbers: CDR0000065777, FHCRC-1205.00, NCI-G97-1331
Study First Received: November 1, 1999
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00003081  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood rhabdomyosarcoma
recurrent adult soft tissue sarcoma
adult rhabdomyosarcoma
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor

Study placed in the following topic categories:
Melphalan
Neuroectodermal Tumors, Primitive
Ewing's family of tumors
Malignant mesenchymal tumor
Osteosarcoma
Osteogenic sarcoma
Recurrence
Soft tissue sarcomas
Thiotepa
Neuroectodermal Tumors
Neoplasms, Connective and Soft Tissue
Ewing's sarcoma
Sarcoma, Ewing's
Peripheral neuroectodermal tumor
Busulfan
Neoplasms, Germ Cell and Embryonal
Sarcoma
Neuroepithelioma
Neuroectodermal Tumors, Primitive, Peripheral
Rhabdomyosarcoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms, Muscle Tissue
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Myosarcoma
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms, Bone Tissue
Therapeutic Uses
Myeloablative Agonists
Neoplasms, Connective Tissue
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009