Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information
Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase II | Treatment | Completed | 30 and under | NCI | POG-9457 CCG-P9457, NCT00002643, P9457 |
Objectives
I. Evaluate the response rate and duration of response of patients with newly diagnosed, metastatic Ewing's sarcoma or primitive neuroectodermal tumor treated with maximally intensified VAdrC (vincristine, doxorubicin, cyclophosphamide) alternating with IE (ifosfamide, etoposide). II. Evaluate the response to new agents (first topotecan, then topotecan with cyclophosphamide) utilized in an upfront treatment window. III. Assess the role of surgery with regard to local control of primary and metastatic sites and disease course. IV. Evaluate whether individual variability in ifosfamide and cyclophosphamide metabolism correlates with toxicity and/or response. V. Evaluate the rise in the absolute neutrophil count following one dose of filgrastim (G-CSF) given immediately prior to a chemotherapy course as an indicator of bone marrow reserve and subsequent myelosuppression. VI. Determine if amifostine provides significant chemo-radio protection, particularly against the cumulative toxicities of this intensive therapy.
Entry Criteria
Disease Characteristics:
Newly diagnosed, pathologically confirmed Ewing's sarcoma or primitive
neuroectodermal tumor (PNET)
Diagnosis established from biopsy of primary tumor
Light microscopy (hematoxylin and eosin stained) consistent with Ewing's
sarcoma or PNET
No immunohistochemical or ultrastructural characteristics inconsistent with
Ewing's sarcoma or PNET or suggestive of rhabdomyosarcoma
Metastatic disease required
Biopsy of radiographically questionable metastases (e.g., pulmonary lesions)
required
Chest wall tumor with separate pleural mass considered metastatic
No positive pleural fluid cytology alone
Prior/Concurrent Therapy:
No prior chemotherapy or radiotherapy Resection at diagnosis is discouraged but does not exclude
Patient Characteristics:
Age:
30 and under
Performance status:
Not specified
Hematopoietic:
(in the absence of marrow involvement)
Absolute neutrophil count greater than 1,200/mm3
Platelet count greater than 120,000/mm3
Hepatic:
Bilirubin less than 1.5 mg/dL
AST/ALT less than 3 times normal
Renal:
Creatinine normal for age
Significant renal abnormality/disease eligible only if:
Nuclear GFR is normal
Study coordinator approves
Cardiovascular:
Echocardiogram or MUGA normal
Expected Enrollment
A total of 130 patients will be accrued to the randomized amifostine amendment over 3 years. A total of 30 patients will be accrued on the investigational window.
Outline
This is a partially randomized, multicenter study. Patients are treated on the investigational window first or proceed to induction therapy immediately, if aggressive treatment is necessary. Investigational window: Patients receive cyclophosphamide IV and topotecan IV over 30 minutes on days 1-5. Filgrastim (G-CSF) is administered subcutaneously (SQ) beginning day 6 until blood cell counts recover. Treatment is repeated at week 3. Induction therapy: Patients over 12 months old are randomized to receive amifostine or not. Patients receive etoposide IV over 45 minutes and ifosfamide IV over 2 hours on days 1-5. Amifostine IV over 15 minutes is also administered prior to ifosfamide. Patients receive G-CSF SQ (or IV over 2 hours) beginning on day 6. This course of treatment is administered on weeks 6, 12, and 18. Patients receive the VAdrC chemotherapy regimen on weeks 9 and 15. This regimen consists of vincristine IV and amifostine IV over 15 minutes on days 1, 8, and 15, cyclophosphamide IV over 30 minutes and doxorubicin IV over 48 hours on days 1 and 2, and G-CSF beginning on day 3. The VAdrC regimen is continued during local therapy on weeks 21-29 and 39-47, except the day 15 dose of vincristine is omitted, cyclophosphamide is administered on day 1 only on weeks 21, 24, 27, 39, 42, and 45, and doxorubicin is replaced with etoposide IV over 60 minutes on days 1-3 on weeks 24, 28, 42, and 45. Local therapy begins after 21 weeks of chemotherapy. Patients who respond to chemotherapy and have resectable disease undergo a complete resection with negative margins. Patients with unresectable disease or bulky lesions undergo radiotherapy. Some patients may undergo both surgery and radiotherapy. Local therapy of metastases is delayed until after week 39. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually thereafter.Published Results
Bernstein ML, Devidas M, Lafreniere D, et al.: Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. J Clin Oncol 24 (1): 152-9, 2006.[PUBMED Abstract]
Souid AK, Newton GL, Dubowy RL, et al.: Determination of the cytoprotective agent WR-2721 (Amifostine, Ethyol) and its metabolites in human blood using monobromobimane fluorescent labeling and high-performance liquid chromatography. Cancer Chemother Pharmacol 42 (5): 400-6, 1998.[PUBMED Abstract]
Related PublicationsSouid AK, Fahey RC, Dubowy RL, et al.: WR-2721 (amifostine) infusion in patients with Ewing's sarcoma receiving ifosfamide and cyclophosphamide with mesna: drug and thiol levels in plasma and blood cells, a Pediatric Oncology Group study. Cancer Chemother Pharmacol 44 (6): 498-504, 1999.[PUBMED Abstract]
Trial Lead Organizations
Pediatric Oncology Group
 | | | |
| Mark Bernstein, MD, FRCPC, Protocol chair(Contact information may not be current) | |
| |
| |||
Children's Cancer Group
| | | ||
| Paul Meyers, MD, Protocol chair | |
| ||
| ||||
| Registry Information | ||
| ||
| Official Title | INTENSIVE THERAPY WITH GROWTH FACTOR SUPPORT FOR PATIENTS WITH EWING'S TUMOR METASTATIC AT DIAGNOSIS: A PEDIATRIC ONCOLOGY GROUP PHASE II STUDY | |
| ||
| Trial Start Date | 1995-04-01 | |
| ||
| Registered in ClinicalTrials.gov | NCT00002643 | |
| ||
| Date Submitted to PDQ | 1995-04-01 | |
| ||
| Information Last Verified | 2007-03-23 | |
| ||
| NCI Grant/Contract Number | U10-CA30969 | |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.
Back to Top
