International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours

• Register: EUCTR
• Last refreshed on: 8 March 2021
• Main ID: EUCTR2012-002107-17-IE
• Date of registration: 10/08/2015
• Prospective Registration: No
• Primary sponsor: University of Birmingham
• Public title: International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours
• Scientific title: International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours - Euro Ewing 2012
• Date of first enrolment: 07/08/2015
• Target sample size: 600
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002107-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Czechia, Denmark, France, Germany, Hungary, Ireland, Italy, Montenegro, Netherlands, Poland, Serbia, Slovakia, Spain, Switzerland, United Kingdom

Contacts

• Name: Jennifer Anderton
• Affiliation: University of Birmingham

• Name: Jennifer Anderton
• Affiliation: University of Birmingham

Key inclusion & exclusion criteria

Inclusion criteria:
• Any histologically and genetically confirmed ESFT of bone or soft tissue, or round cell sarcomas 'Ewing's-like'
but which are negative for EWSR1 gene rearrangement.
• Age >2 years and <50 years (from second birthday to 49 years 364 days) at the date of diagnostic biopsy
• Randomisation =45 days after diagnostic biopsy/surgery
• Patient assessed as medically fit to receive the treatment in either of the R1 treatment arms
• No prior treatment for ESFT other than surgery
• Documented negative pregnancy test for female patients of childbearing potential
• Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where applicable
• Written informed consent from the patient and/or the parent/legal guardian
Are the trial subjects under 18? yes
Number of subjects for this age range: 470
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Contra-indication to the treatment in either of the R1 treatment arms
• Second malignancy
• Pregnant or breastfeeding women
• Follow-up not possible due to social, geographic or psychological reasons


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ewing's Sarcoma Family of Tumours
MedDRA version: 20.0 Level: PT Classification code 10015560 Term: Ewing's sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Doxorubicin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Doxorubicin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: Etoposide
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Etoposide
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Vincristine
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Product Name: Ifosfamide
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Ifosfamide
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Actinomycin D
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Dactinomycin
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-

Product Name: Zoledronic Acid
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Zoledronic acid
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 0.04 0.8-

Trade Name: Busilvex
Product Name: Busilvex
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: BUSULFAN
Current Sponsor code: C6 H14 O6 S2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Melphalan
Product Name: Melphala

Primary Outcome(s)

Main Objective: The objective of the induction/consolidation chemotherapy randomisation (R1) is to compare the VIDE strategy (VIDE induction and VAI/VAC/BuMel consolidation) with the VDC/IE/BuMel strategy (compressed VDC/IE induction and IE/VC consolidation). The event-free survival (EFS) of the two chemotherapy regimens will be compared, and also the relative toxicity experienced by patients both before and after local control.

Timepoint(s) of evaluation of this end point: For each randomisation, EFS is defined as the time from randomisation to first event, where an event is progression without complete remission, recurrence (following complete remission), diagnosis of second malignancy or death. Patients who have not had an event will be censored at their last follow up date. Patients lost to follow up without an event will be censored at the date of their last consultation.

Primary end point(s): Event free survival (EFS)

Secondary Objective: The objective of the zoledronic acid randomisation (R2) is to determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome.

Secondary Outcome(s)

Secondary end point(s): • Overall Survival (OS)
• Adverse events and toxicity, defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0
• Histological response of the primary tumour to induction chemotherapy if surgery is performed as local control.
• Response of primary tumour, regional lymph nodes and/or metastases
• Achievement of local control at the end of treatment
• Growth parameters and jaw/ear osteonecrosis (R2 only)

Timepoint(s) of evaluation of this end point: • Overall Survival (OS)- evaluated continually
• Adverse events and toxicity – evaluated after each course of chemotherapy, or as reported
• Histological response if surgery is performed – evaluated at the time of surgery following induction chemotherapy
• Response of primary tumour, regional lymph nodes and/or metastases - evaluated after cycle 2 or 3,before local control and end of treatment.
• Achievement of local control at the end of treatment – evaluated at the time of surgery following induction
chemotherapy or at the end of treatment or six months after the end of treatment
• Growth parameters (R2 only)– evaluated at baseline, end of treatment and at follow up
• Jaw/ear osteonecrosis (R2 only)– evaluated during or at end of treatment

Secondary ID(s)

2012-002107-17-GB

ISRCTN92192408

RG_11-152

Source(s) of Monetary Support

CTAAC

Ethics review

Status: Approved
Approval date: 07/07/2015
Contact: