Combination Chemotherapy Plus Surgery and Radiation Therapy in Treating Patients With Ewing's Sarcoma

September 16, 2013 updated by: University Hospital Muenster

EUROPEAN INTERGROUP COOPERATIVE EWING'S SARCOMA STUDY [EICESS 92]

RATIONALE: Drugs used in chemotherapy use 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. Combining more than one drug with surgery and radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective in treating patients with Ewing's sarcoma.

PURPOSE: Randomized phase III trial to compare various combination chemotherapy regimens plus surgery and radiation therapy in treating patients who have Ewing's sarcoma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine whether morbidity can be reduced while preserving survival by substituting cyclophosphamide for ifosfamide in adjuvant combination chemotherapy in standard-risk patients with Ewing's sarcoma or peripheral neuroectodermal tumor (PNET). II. Determine whether survival is improved without unacceptable toxicity for high-risk patients with Ewing's sarcoma or PNET by the addition of etoposide to the VAIA regimen (vincristine/doxorubicin/ifosfamide/dactinomycin). III. Evaluate the impact of surgery and conventional vs. hyperfractionated radiotherapy (definitive and adjuvant) on local control, overall survival, and morbidity in these patients. IV. Relate treatment outcome with patient characteristics, histologic subtype at diagnosis, and histologic response to neoadjuvant treatment. V. Evaluate prospectively ifosfamide-induced nephrotoxicity and doxorubicin-induced cardiotoxicity.

OUTLINE: Randomized study. Patients are initially stratified as STANDARD RISK (tumor volume at diagnosis < 100 ml) and HIGH RISK (tumor volume at diagnosis at least 100 ml or, if < 100 ml, metastasis present). All patients receive 14 courses of chemotherapy, administered q 3 weeks throughout protocol treatment. Standard-risk patients receive 4 courses of NEOADJUVANT CHEMOTHERAPY on Regimen A, while high-risk patients are randomized on Arms I and II for 4 courses of neoadjuvant chemotherapy. LOCAL THERAPY is usually initiated on week 12, after 4 courses of neoadjuvant chemotherapy, and consists of either total removal of the tumor-bearing compartment, intracompartmental surgery (with or without adjuvant radiotherapy), or definitive radiotherapy alone; the choice is dictated by the site, tumor size, and patient age, among other variables. Postoperatively, all patients receive 10 courses of ADJUVANT CHEMOTHERAPY (plus adjuvant radiotherapy when given); standard-risk patients are randomized on Arms III and IV, while high-risk patients receive the same regimen to which they were assigned at initial randomization. When given, adjuvant radiotherapy begins on week 19 and is administered concurrently with chemotherapy. As a variant of this general plan, patients with < 50% regression of the soft tissue component of their tumors at restaging after 2 courses of neoadjuvant chemotherapy (slow response) may receive preoperative irradiation, beginning on week 7, concomitantly with the third and fourth courses of chemotherapy. The following acronyms are used: CTX Cyclophosphamide, NSC-26271 DACT Dactinomycin, NSC-3053 DOX Doxorubicin, NSC-123127 IFF Ifosfamide, NSC-109724 Mesna Mercaptoethane sulfonate, NSC-113891 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 NEOADJUVANT CHEMOTHERAPY. Regimen A (Standard risk): Alternating 3-Drug Combination Chemotherapy Regimens. VAIA: VCR/DOX/IFF alternating with VCR/DACT/IFF. Arm I (High risk): Alternating 3-Drug Combination Chemotherapy Regimens. VAIA: VCR/DOX/IFF alternating with VCR/DACT/IFF. Arm II (High-risk): Alternating 4-Drug Combination Chemotherapy Regimens. EVAIA: VP-16/VCR/DOX/IFF alternating with VP-16/VCR/DACT/IFF. LOCAL THERAPY. Surgery: Resection of entire tumor-bearing compartment, including bone and soft tissue, when possible, is the treatment of choice. The range of possible surgical procedures includes: radical resection (e.g., amputation), wide resection (en bloc removal of the entire tumor-bearing compartment), marginal surgery (en bloc removal, but resection line runs through pseudocapsule and microscopic residual disease is likely), intralesional resection (tumor incised with contamination of surgical field), and no resection. Radiotherapy: There are 3 settings in which radiotherapy is delivered in these patients: as definitive treatment when definitive surgery is not feasible, as postoperative adjuvant treatment, and preoperatively in patients with a slow response to neoadjuvant chemotherapy. Patients who are to receive definitive and postoperative adjuvant treatment are randomized between conventional fractionation and hyperfractionated accelerated split-course delivery; individuals receiving preoperative irradiation are not randomized for radiotherapy schedule but are assigned nonrandomly to receive the hyperfractionated accelerated split-course scheme (conventional fractionation requires that DOX and DACT be eliminated from concomitant chemotherapy, whereas these agents can be continued during the hyperfractionated schedule). Individual institutions may elect not to randomize for the radiotherapy fractionation scheme, i.e., to treat all patients on one schedule or the other; in such institutions, all patients must follow the same scheme, decided upon prior to treatment of the first patient. Use of photons with energies of 4-6 MV (including Co60) is recommended for extremity lesions, and 6-15 MV energies are recommended for trunk lesions; electrons may be considered for small superficial boosts, but are not adequate as a sole modality. ADJUVANT THERAPY. Arm III (Standard risk): Alternating 3-Drug Combination Chemotherapy Regimens. VACA: VCR/DOX/CTX alternating with VCR/DACT/CTX. Arm IV (Standard risk): Alternating 3-Drug Combination Chemotherapy Regimens. VAIA: VCR/DOX/IFF alternating with VCR/DACT/IFF. High-risk patients continue with 10 additional courses of VAIA or EVAIA according to original randomization. Adjuvant Radiotherapy, when administered, begins on week 19, and is given concomitantly with chemotherapy.

PROJECTED ACCRUAL: It is anticipated that 600 patients (200 standard-risk and 400 high-risk) will be accrued over 4 years.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • Newcastle-upon-Tyne, England, United Kingdom, NE1 4LP
        • Royal Victoria Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 35 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Biopsy-proven Ewing's sarcoma, atypical Ewing's sarcoma, and peripheral neuroectodermal tumors No soft tissue Ewing's sarcoma or other small cell sarcomas of soft tissue Such patients should be treated on the appropriate national Soft Tissue Sarcoma Protocol Treatment must begin within 3 weeks after diagnostic biopsy Registration must occur within 6 weeks after initiation of treatment

PATIENT CHARACTERISTICS: Age: Not over 35

PRIOR CONCURRENT THERAPY: No prior therapy, including primary definitive local therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Muenster

Collaborators

Medical Research Council

Investigators

  • Study Chair: Alan W. Craft, MD, Newcastle-upon-Tyne Hospitals NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 1992

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

May 4, 2004

First Posted (ESTIMATE)

May 5, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

September 17, 2013

Last Update Submitted That Met QC Criteria

September 16, 2013

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000078196
  • GER-GPOH-EICESS-92
  • MRC-EICESS-92
  • EU-92030
  • EU-205116
  • UKCCSG-ET1993-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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