Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing's Sarcoma

NCT00334867 | Withdrawn Phase 3

• 3 other identifiers: AEWS0531COG-AEWS0531CDR0000483611
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating Ewing's sarcoma. PURPOSE: This randomized phase III trial is studying combination chemotherapy and topotecan to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed localized Ewing's sarcoma.

Conditions

Sarcoma

Keywords

localized Ewing sarcoma/peripheral primitive neuroectodermal tumor

Outcome Measures

Primary Outcomes (1)

• Event-free survival

Secondary Outcomes (1)

• Survival form study enrollment

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and 16. Patients undergo local therapy comprising conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19.

Drug: cyclophosphamide; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: radiation therapy

Arm II

EXPERIMENTAL

Patients receive vincristine sulfate IV over 1 minute once a week on day 1 in weeks 1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1 hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 7 and 16. Patients also undergo local therapy comprising of conventional surgery (surgical resection) in approximately week 18 and/or radiation therapy beginning in approximately week 19. Patients then proceed to combination chemotherapy.

Drug: cyclophosphamide; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: topotecan hydrochloride; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: radiation therapy

Interventions

cyclophosphamide DRUG

Given IV

Arm I; Arm II

dexrazoxane hydrochloride DRUG

Given IV

Arm I; Arm II

doxorubicin hydrochloride DRUG

Given IV

Arm I; Arm II

etoposide DRUG

Given IV

Arm I; Arm II

ifosfamide DRUG

Given IV

Arm I; Arm II

topotecan hydrochloride DRUG

Given IV

Arm II

vincristine sulfate DRUG

Given IV

Arm I; Arm II

conventional surgery PROCEDURE

Patients undergo surgery in week 18

Arm I; Arm II

radiation therapy PROCEDURE

Patients undergo radiation therapy in week 19

Arm I; Arm II

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically and cytologically confirmed extracranial Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue * Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural-based secondary tumor nodules allowed * Contralateral pleural effusions or pleural nodules are not eligible * Tumor arising in the bony skull (extradural) are eligible * Tumors arising in the intradural soft tissue are not eligible * Newly diagnosed disease * Only have had a biopsy of the primary tumor without an attempt at complete or partial resection * Prior attempted or accomplished unplanned excision allowed provided adequate imaging was obtained prior to surgery AND resection considered incomplete and further local control required * No evidence of metastatic disease, defined as lesions discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor * No evidence of metastatic lung disease by CT scan * One pulmonary nodule \> 1 cm in diameter OR \> 1 nodule \> 0.5 cm in diameter are considered evidence of pulmonary metastasis * Solitary nodules 0.5-1.0 cm or multiple nodules 0.3-0.5 cm must be confirmed negative by biopsy * Solitary nodules \< 0.5 cm or multiple nodules \< 0.3 cm not considered clear evidence of lung disease * No distant nodule disease * No esthesioneuroblastoma PATIENT CHARACTERISTICS: * Performance status (PS) 0-2 (Karnofsky PS 50-100% for patients ≥ 16 years of age or Lansky PS 50-100% for patients \< 16 years of age) * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST or ALT \< 2.5 times ULN * Shortening fraction ≥ 27% by EKG * Ejection fraction ≥ 50% by radionuclide angiogram * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior radiotherapy * No prior chemotherapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Cyclophosphamide; Dexrazoxane; Doxorubicin; Etoposide; Ifosfamide; Topotecan; Vincristine; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Camptothecin; Alkaloids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Therapeutics

Study Officials

• Mason Bond, MD

  Children's & Women's Hospital of British Columbia

  STUDY CHAIR

• Leo Mascarenhas, MD

  Children's Hospital Los Angeles

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2006
• First Posted: June 8, 2006
• Study Start: December 1, 2005
• Primary Completion: January 1, 2006
• Last Updated: June 28, 2013

Record last verified: 2013-06