Study in Localized and Disseminated Ewing Sarcoma (EWING 2008)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2009 by University Hospital Muenster
Sponsor:
Information provided by:
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT00987636
First received: September 30, 2009
Last updated: November 17, 2009
Last verified: September 2009
  Purpose

Ewing Sarcoma

Primary objectives:

Standard Risk R1: in a randomised trial, to examine whether add-on treatment with fenretinide or zoledronic acid, or zoledronic acid plus fenretinide in addition to induction and maintenance chemotherapy improves event-free survival in patients with localised Ewing sarcoma and good histological response or with initial tumour volume < 200ml compared to no add on treatment.

High Risk R2: in a randomised trial, to examine whether high dose chemotherapy using busulfan-melphalan with autologous stem cell reinfusion, compared with standard chemotherapy, improves event-free survival in patients with localised Ewing sarcoma and unfavourable histological response or tumour volume>200ml (R2loc). In patients with pulmonary metastases high dose busulfan-melphalan chemotherapy with autologous stem cell reinfusion is randomised versus standard chemotherapy plus whole lung irradiation (R2pulm).

Very High Risk R3: in a randomised trial, to examine whether the addition of high dose chemotherapy using treosulfan-melphalan followed by autologous stem cell reinfusion to eight cycles of standard adjuvant chemotherapy, compared to eight cycles of standard adjuvant chemotherapy alone, improves event-free survival in patients with primary disseminated disease.


Condition Intervention Phase
Ewing's Sarcoma
Drug: Zoledronic acid
Drug: Busulfan
Drug: Treosulfan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • Event free survival [ Time Frame: 6.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 6.5 years ] [ Designated as safety issue: No ]
  • safety and toxicity [ Time Frame: permanent ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: 8.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 1383
Study Start Date: October 2009
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R1
Standard Risk R1: in a randomised trial, to examine whether add-on treatment with fenretinide or zoledronic acid, or zoledronic acid plus fenretinide in addition to induction and maintenance chemotherapy improves event-free survival in patients with localised Ewing sarcoma and good histological response or with initial tumour volume <200ml compared to no add on treatment.
Drug: Zoledronic acid

intravenously at 28 day intervals beginning with cycle 6 of VAC/VAI consolidation chemotherapy for a total period of nine months.

Patients < 18 years will receive 0.05 mg/kg BW by IV infusion 30 min-1 h.

Patients >= 18 years will receive a bodyweight-dependent dose:

Patients >40kg receive 4 mg by IV infusion 30 min-1h Patients 20-40 kg receive 2 mg by IV infusion 30 min-1h

Other Names:
  • Zometa
  • Bisphosphonate
Experimental: R2
High Risk R2: in a randomised trial, to examine whether high dose chemotherapy using busulfan-melphalan with autologous stem cell reinfusion, compared with standard chemotherapy, improves event-free survival in patients with localised Ewing sarcoma and unfavourable histological response or tumour volume>200ml (R2loc). In patients with pulmonary metastases high dose busulfan-melphalan chemotherapy with autologous stem cell reinfusion is randomised versus standard chemotherapy plus whole lung irradiation (R2pulm).
Drug: Busulfan
intravenously, day -6 to d -3 adults: 0.8 mg/kg body weight (BW) children and adolescents: <9 kg= 1mg/kg BW 9 - <16 kg= 1.2 mg/kg BW 16 - 23 kg= 1.1 mg/kg BW >23 - 34 kg= 0.95 mg/kg BW >34 kg = 0.8 mg/kg BW
Other Name: Busilvex
Experimental: R3
Very High Risk R3: in a randomised trial, to examine whether the addition of high dose chemotherapy using treosulfan-melphalan followed by autologous stem cell reinfusion to eight cycles of standard adjuvant chemotherapy, compared to eight cycles of standard adjuvant chemotherapy alone, improves event-free survival in patients with primary disseminated disease.
Drug: Treosulfan
12 g/m² d-5 to d-3

Detailed Description:

EWING 2008 is a joint protocol of European and North American Ewing sarcoma study groups. The protocol is aimed at optimising treatment and treatment results of patients with Ewing sarcomas. The EWING 2008 protocol is open to all patients diagnosed with Ewing sarcomas, localised or metastatic, who are considered eligible for neoadjuvant chemotherapy. All patients registered will receive induction chemotherapy consisting of six cycles of vincristine, ifosfamide, doxorubicin and etoposide (VIDE). The decision regarding local therapy must be made following the fifth cycle of induction treatment, with a preference for surgical intervention with or without additional radiotherapy. Preoperative radiotherapy may be considered to improve the operability of otherwise inoperable lesions. In patients with localised disease or with pulmonary metastases, local treatment should be performed following the 6th cycle of VIDE chemotherapy, and should be a complete tumour resection, whenever feasible. Post-operative radiotherapy is determined by the completeness of surgery and the histological response to chemotherapy.

Standard Risk R1 Good responders (R1) (< 10% viable tumour cells) with localised disease are allocated to the standard risk arm and will receive a further eight cycles of chemotherapy composed of vincristine, actinomycin D, and cyclophosphamide (VAC) (females) or ifosfamide instead of cyclophosphamide (VAI) (males). They will be randomised to receive add-on treatment with either fenretinide, zoledronic acid, fenretinide plus zoledronic acid, or no add-on treatment.

High Risk R2 Poor responders (R2) with localised disease will continue to be randomised as in EURO-E.W.I.N.G. 99 to receive either eight cycles of VAI chemotherapy or high dose treatment with busulfan-melphalan (R2loc).

Patients with primary pulmonary metastases are also allocated to continue to be randomised as in EURO-E.W.I.N.G. 99 to receive either eight cycles of VAI chemotherapy or high dose treatment with busulfan-melphalan (R2pulm).

Very High Risk R3 Patients with disseminated disease, i.e. dissemination to bone and/or other sites and possibly additional pulmonary dissemination (R3), receive six cycles of VIDE induction chemotherapy. Patients are then randomised to either continue with eight cycles of vincristine, actinomycin D and cyclophosphamide (VAC) chemotherapy or high dose treosulfan-melphalan (TreoMel) chemotherapy followed by autologous stem cell reinfusion followed thereafter by eight cycles of VAC chemotherapy. Local therapy in R3 patients is following VIDE induction, whenever feasible prior to high dose therapy (HDT). When long periods of immobilisation following surgery are anticipated, e.g pelvic reconstruction, surgery following HDT may be advisable. Depending on clinical response to induction chemotherapy radiotherapy prior to HDT and surgery may be an option to be considered in such patients. Any delay between VIDE and HDT for reasons of e.g. local treatment must be bridged with VAC cycles. The total number of VAC cycles is not to exceed eight cycles.

  Eligibility

Ages Eligible for Study:   48 Months to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis: Histologically confirmed Ewing sarcoma of bone or soft tissue.
  • Age and sex: Either sex, age >48 months (for GPOH patients) and <50 years at the date of diagnostic biopsy. Younger or elderly patients may be reported to the appropriate office (see section 1.4) but are not included in this study.
  • Registration: ≤ 45 days after diagnostic biopsy/surgery.
  • Start of chemotherapy: ≤ 45 days after diagnostic biopsy/surgery.
  • Informed consent: Must be signed prior to study entry.
  • Performance status: Lansky or Karnofsky score > 50%, may be modified for handicapped patients.
  • Haematological parameters:

    • Haemoglobin > 8 g/dl (transfusion allowed),
    • Platelets > 80.000/µl (transfusion allowed),
    • WBC > 2000/µl.
  • Cardiac values: LVEF > 40%, SF > 28%.

Exclusion Criteria:

  • More than one cycle of other chemotherapy prior to registration
  • Second malignancy
  • Pregnancy and lactation
  • Concurrent treatment within any other clinical trial, except trials with different endpoints that due to the nature of their endpoints must run parallel to EWING 2008 e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support, etc...
  • Any other medical, psychiatric, or social condition incompatible with protocol treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987636

Contacts
Contact: Uta Dirksen, MD PhD +49251 ext 8356485 uta.dirksen@ukmuenster.de
Contact: Heribert Juergens, MD, Prof. +49251 ext 8347742 jurgh@uni-muenster.de

Locations
Germany
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie - Recruiting
Münster, Germany, 48149
Principal Investigator: Heribert Juergens, Professor, MD         
Sub-Investigator: Uta Dirksen, MD, PhD         
Sub-Investigator: Birgit Froehlich, MD         
Sponsors and Collaborators
University Hospital Muenster
Investigators
Study Chair: Heribert Juergens, MD, Prof Universitätsklinikum Münster
Study Chair: Alan W Craft, Professor, Sir, MD The Royal Victoria Infirmary, Institute of Child Health
Principal Investigator: Heribert Juergens, Professor, MD Universitätsklinikum Münster Klinik und Poliklinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie
  More Information

No publications provided

Responsible Party: University Hospital Münster
ClinicalTrials.gov Identifier: NCT00987636     History of Changes
Other Study ID Numbers: 108128, EudraCT number: 2008-003658-13
Study First Received: September 30, 2009
Last Updated: November 17, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut

Keywords provided by University Hospital Muenster:
Ewing Sarcoma
localized
disseminated
metastases
bone
soft tissue

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Osteosarcoma
Busulfan
Treosulfan
Zoledronic acid
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Bone Density Conservation Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014