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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00987636
Other study ID # 108128
Secondary ID 2008-003658-13
Status Completed
Phase Phase 3
First received
Last updated
Start date October 1, 2009
Est. completion date March 31, 2019

Study information

Verified date October 2019
Source University Hospital Muenster
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Ewing Sarcoma

Primary objectives:

Standard Risk R1: in a randomised trial, to examine whether add-on treatment with zoledronic acid 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 <200 mL 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 poor histological response or tumour volume ≥200 mL (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.

*R2 accrual discontinued on December 1st 2015.


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.

*R2 accrual discontinued on December 1st 2015.


Recruitment information / eligibility

Status Completed
Enrollment 907
Est. completion date March 31, 2019
Est. primary completion date March 31, 2019
Accepts healthy volunteers No
Gender All
Age group 48 Months to 50 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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
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
Treosulfan
12 g/m² d-5 to d-3

Locations

Country Name City State
Germany University Hopital Essen, Pediatrics III, Hematology/ Oncology, Sarcoma Centre, International Ewing Sarcoma Study Group, West German Cancer Centre Essen
Germany University Children´s Hospital, Pediatric Hematology and Oncology Muenster

Sponsors (1)

Lead Sponsor Collaborator
University Hospital Muenster

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Event free survival 9.5 years
Secondary Overall survival 9.5 years
Secondary Safety and toxicity permanent
Secondary Quality of life 9.5 years
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