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

• Register: EUCTR
• Last refreshed on: 1 December 2014
• Main ID: EUCTR2012-002107-17-ES
• Date of registration: 06/08/2014
• 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: 25/11/2014
• 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

Countries of recruitment

France, Ireland, Israel, Spain, United Kingdom, United States

Contacts

• Name: Melissa Fernández
• Affiliation: Grupo Español de Investigación en Sarcomas (GEIS)

• Name: Melissa Fernández
• Affiliation: Grupo Español de Investigación en Sarcomas (GEIS)

Key inclusion & exclusion criteria

Inclusion criteria:
? Histologically confirmed ESFT of bone or soft tissue
? Localised or pulmonary and/or pleural metastatic disease
? 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 0

Exclusion criteria:
? Extrapulmonary metastatic disease
? 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: 17.0 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: Vincristina
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
CAS Number: 57-22-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Product Name: Ifosfamida
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: Doxorrubicina
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Doxorubicin
CAS Number: 23214-92-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: Etopósido
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: Actinomicina 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: Ciclofosfamida
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: Ácido zoledrónico
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)

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

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 in patients with localised ESFT or with pulmonary and/or pleural metastases only at diagnosis.

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 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.
? Primary tumour and lung and/or pleural metastases response
? Achievement of local control at the end of treatment
? Growth parameters and jaw 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 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 ID(s)

2012-002107-17-GB

ISRCTN92192408

RG_11-152

Source(s) of Monetary Support

CTAAC