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Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma

Phase 3
48 Months
50 Years
Open (Enrolling)
Ewing's Sarcoma

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Trial Information

Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma

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.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event free survival

Outcome Time Frame:

6.5 years

Safety Issue:


Principal Investigator

Heribert Juergens, MD, Prof

Investigator Role:

Study Chair

Investigator Affiliation:

Universitätsklinikum Münster


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

October 2009

Completion Date:

March 2018

Related Keywords:

  • Ewing's Sarcoma
  • Ewing Sarcoma
  • localized
  • disseminated
  • metastases
  • bone
  • soft tissue
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma