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

• Register: EUCTR
• Last refreshed on: 6 February 2017
• Main ID: EUCTR2012-002107-17-CZ
• Date of registration: 03/06/2015
• 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: 15/09/2015
• 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

Belgium, Czech Republic, 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 EWSRl 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 Rl 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 Rl
• Contra-indication to the treatment in either of the Rl 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.
* 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

Ewing's Sarcoma Family of Tumours
MedDRA version: 19.1 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: 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-

Primary Outcome(s)

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.

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.

Main Objective: The objective of the induction/consolidation chemotherapy randomisation (R1) is to compare the VIDE strategy (VIDE induction and VAI/VAC consolidation) with the VDC/IE 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 of the primary tumour.

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

Secondary Outcome(s)

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 of the primary tumour to induction chemotherapy if surgery is performed as local control – evaluated at the time of surgery following induction chemotherapy
• Primary tumour and lung and/or pleural metastases response-evaluated after 2 cycles (Arm A), or 3 cycles (Arm B).
• 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 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)

Secondary ID(s)

RG_11-152

1402-STBSG

2012-002107-17-GB

ISRCTN92192408

Source(s) of Monetary Support

FP7

CTAAC