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

• Register: EUCTR
• Last refreshed on: 7 June 2021
• Main ID: EUCTR2012-002107-17-NL
• Date of registration: 21/12/2015
• Prospective Registration: Yes
• 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: 22/09/2016
• 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

Belgium, Czech Republic, Denmark, Hungary, Ireland, Netherlands, Spain, United Kingdom

Contacts

• Name: Jennifer Anderton
• Affiliation: University of Birmingham

• Name: Jennifer Anderton
• Affiliation: University of Birmingham

Key inclusion & exclusion criteria

Inclusion criteria:
Randomisation R1:
* Any histologically and genetically confirmed ESFT of bone or soft tissue, or round cell sarcomas which are ‘Ewing’s-like’ but negative for EWSR1 gene rearrangement
* Age >2 years and <50 years (from second birthday to 49 years 364 days) at the date of randomisation
* 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

Randomisation 2:
* Age >5 years (from fifth birthday) at date of randomisation
* Localised tumour
OR
* Metastatic disease and/or regional lymph node(s) involvement only at diagnosis and at least partial response of the metastases and/or regional lymph node(s)
* Consolidation chemotherapy as per protocol intended
* Patient assessed as medically fit to receive zoledronic acid if allocated
* 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 0

Exclusion criteria:
Randomisation R1
• 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
Randomisation 2:
* History of dental surgery (extraction or jaw surgery) in the 6 months preceding the start of zoledronic acid treatment, or planned dental surgery within the treatment period or within 6 months after the end of treatment.
*History of jaw fracture
* Ewing’s tumour of the maxilla or of the mandible
* Progression of the primary tumour or appearance of new lesions


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

Health Condition(s) or Problem(s) studied

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

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)

Intervention(s)

Product Name: Vincristine
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
CAS Number: 2068-78-2
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
CAS Number: 3778-73-2
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Doxorubicin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Doxorubicin
CAS Number: 25316-40-9
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
CAS Number: 33419-42-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Actinomycin D
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Dactinomycin
CAS Number: 50-76-0
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-

Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
CAS Number: 50-18-0
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Zoledronic acid
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Zoledronic acid
CAS Number: 118072-93-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.04-

Product Name: Busulfan
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Busulfan
CAS Number: 55-98-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentrat

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 strategy (compressed VDC/IE induction and IE/VC/Bu-Mel 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 of the primary tumour.

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.

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.

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

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: • OS – evaluated continually
• Adverse events and toxicity – evaluated after each course of chemotherapy, or as reported
• Histological response of the primary tumour to induction chemotherapy if surgery is performed as local control – evaluated at the time of surgery following induction chemotherapy
• Response of primary tumour, regional lymph nodes and/or metastases -evaluated after cycle 2&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 osteonecrosis (R2 only)– evaluated at the end of or during treatment

Secondary ID(s)

2012-002107-17-GB

1402-STBSG

ISRCTN92192408

RG_11-152

Source(s) of Monetary Support

CTAAC

FP7

Ethics review

Status: Approved
Approval date: 22/09/2016
Contact: