Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing's Sarcoma or Neuroectodermal Tumor
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| ClinicalTrials.gov Identifier: NCT00006734 |
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Recruitment Status :
Completed
First Posted : January 27, 2003
Last Update Posted : May 17, 2013
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which chemotherapy regimen combined with radiation therapy and/or surgery is more effective in treating Ewing's sarcoma or primitive neuroectodermal tumor.
PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy regimens combined with radiation therapy and/or surgery in treating patients who have Ewing's sarcoma or primitive neuroectodermal tumor.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sarcoma | Biological: filgrastim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: vincristine sulfate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: brachytherapy Radiation: radiation therapy | Phase 3 |
OBJECTIVES:
- Compare the effect of interval-compressed vs standard chemotherapy in terms of event-free survival and overall survival in patients with newly diagnosed, localized Ewing's sarcoma or peripheral primitive neuroectodermal tumor.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 18 years vs 18 years and over) and location of primary disease (pelvic vs nonpelvic). Patients are randomized to 1 of 2 treatment arms for induction and continuation therapy.
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Induction therapy (weeks 1-12):
- Arm I: Patients receive alternating courses of chemotherapy consisting of vincristine IV on day 1, doxorubicin IV continuously over 48 hours on days 1 and 2, and cyclophosphamide IV over 1 hour on day 1 for courses 1 and 3 and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 for courses 2 and 4. Beginning 24 hours after the last dose of chemotherapy for each course, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Treatment continues every 3 weeks for 4 courses.
- Arm II: Patients receive alternating courses of chemotherapy consisting of vincristine, doxorubicin, and cyclophosphamide as in arm I for courses 1, 3, and 5 and ifosfamide and etoposide as in arm I for courses 2, 4, and 6. Patients also receive G-CSF as in arm I. Treatment continues every 2 weeks for 6 courses.
After completion of induction therapy, patients in both arms receive local control treatment to the primary tumor. Patients receive continuation chemotherapy after surgery or concurrently with radiotherapy.
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Continuation therapy:
- Arm I (weeks 13-42): Patients receive additional alternating courses of chemotherapy as in arm I of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 7 and/or 11 and/or 13. Patients also receive G-CSF as in induction therapy. Treatment continues every 3 weeks for 10 courses.
- Arm II (weeks 13-29): Patients receive additional alternating courses of chemotherapy as in arm II of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 9 and/or 11 and/or 13. Patients also receive G-CSF as in induction therapy. Treatment continues every 2 weeks for 8 courses.
Patients are followed every 3 months for 4 years and then every 6 months for 1 year.
PROJECTED ACCRUAL: Approximately 528 patients will be accrued for this study within 4-5 years.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 587 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Trial of Chemotherapy Intensification Through Compression in Ewing's Sarcoma and Related Tumors |
| Study Start Date : | May 2001 |
| Actual Primary Completion Date : | August 2006 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Regimen A
Test the hypothesis that chemotherapy given every two weeks (Regimen B) will produce higher event-free survival. Treatment will occur in two phases: Induction and Continuation, with 14 cycles of chemotherapy in all. Induction consists of the first twelve weeks (four cycles on Regimen A. The cycles alternate between vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, MESNA and ifosfamide, etoposide, MESNA. G-CSF (Filgrastim) is given between chemotherapy doses. Local control (Surgery, Radiation Therapy, or a combination) will begin on Week 13 which will be after four cycles of chemotherapy.
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Biological: filgrastim
Given IV
Other Names:
Drug: cyclophosphamide Given IV
Other Names:
Drug: doxorubicin hydrochloride Given IV
Other Names:
Drug: etoposide Given IV
Other Names:
Drug: ifosfamide Given IV
Other Names:
Drug: vincristine sulfate Given IV
Other Names:
Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: brachytherapy Radiation: radiation therapy |
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Experimental: Regimen B
Conventional every-three-week chemotherapy for patients with Ewing sarcoma and related tumors. Treatment will occur in two phases: Induction and Continuation, with 14 cycles of chemotherapy in all. Induction consists of the first twelve weeks six cycles on Regimen B). The cycles alternate between vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, MESNA and ifosfamide etoposide MESNA. G-CSF (Filgrastim) is given between chemotherapy doses. Local control (surgery, Radiation Therapy, or a combination) will begin on Week 13, which will be after six cycles of chemotherapy.
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Biological: filgrastim
Given IV
Other Names:
Drug: cyclophosphamide Given IV
Other Names:
Drug: doxorubicin hydrochloride Given IV
Other Names:
Drug: etoposide Given IV
Other Names:
Drug: ifosfamide Given IV
Other Names:
Drug: vincristine sulfate Given IV
Other Names:
Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: brachytherapy Radiation: radiation therapy |
- Event-free survival [ Time Frame: Time from study entry until disease progression, death without progression of disease, occurrence of a second malignant neoplasm or last follow-up, whichever comes first, assessed up to 5 years ]Assessed using a two sided log rank test of 0.05.
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| Ages Eligible for Study: | up to 50 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed localized Ewing's sarcoma or peripheral primitive neuroectodermal tumor (PNET) of the bone or soft tissues
- Diagnostic biopsy of primary tumor within 30 days of study
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Paraspinal or bony skull tumors of extradural origin allowed
- No intradural soft tissue tumors
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Askin's tumor of the chest wall allowed
- Chest wall tumors with ipsilateral pleural effusions or ipsilateral pleural-based secondary tumor nodules allowed
- No contralateral pleural effusions
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No metastatic disease or distant node involvement
- One pulmonary or pleural nodule greater than 1 cm in diameter OR more than 1 nodule greater than 0.5 cm in diameter are considered pulmonary metastasis
- Solitary lung nodules of 0.5-1 cm OR multiple nodules of 0.3-0.5 cm allowed unless biopsy positive for tumor
- Light microscopic appearance (hematoxylin and eosin stained) consistent with Ewing's sarcoma or peripheral PNET
- No immunohistochemical or ultrastructural evidence of rhabdomyosarcoma
- No esthesioneuroblastoma
- Clinically or pathologically involved regional lymph nodes allowed
- No CNS involvement
PATIENT CHARACTERISTICS:
Age:
- 50 and under at diagnosis
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
Renal:
- Creatinine normal for age
- Creatinine clearance or isotope glomerular filtration rate at least 75 mL/min
Cardiovascular:
- Shortening fraction at least 28% by echocardiography OR
- Ejection fraction at least 55% by radionuclide angiogram
Other:
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No other prior malignancy except skin cancer diagnosed at least 5 years ago and currently in remission
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior immunotherapy for skin cancer
- No concurrent sargramostim (GM-CSF)
- No concurrent pegfilgrastim
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior radiotherapy
Surgery:
- Prior complete or partial excision of primary tumor allowed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006734
Show 239 study locations
| Study Chair: | Richard B. Womer, MD | Children's Hospital of Philadelphia |
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00006734 |
| Other Study ID Numbers: |
AEWS0031 COG-AEWS0031 ( Other Identifier: Children's Oncology Group ) CDR0000068323 ( Other Identifier: Clinical Trials.gov ) A7983 ( Other Identifier: Children's Cancer Group ) |
| First Posted: | January 27, 2003 Key Record Dates |
| Last Update Posted: | May 17, 2013 |
| Last Verified: | May 2013 |
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localized Ewing sarcoma/peripheral primitive neuroectodermal tumor |
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Sarcoma Sarcoma, Ewing Neuroectodermal Tumors Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Osteosarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Cyclophosphamide Ifosfamide Doxorubicin Liposomal doxorubicin |
Etoposide Vincristine Lenograstim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors |