Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
vn 0.4, vd 06-Jan-2014
Study information
Scientific title
rEECur: an international randomised controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma
Acronym
rEECur
Study hypothesis
To compare four chemotherapy regimens: topotecan and cyclophosphamide (TC); irinotecan and temozolomide (IT); gemcitabine and docetaxel (GD) and high-dose ifosfamide (IFOS) in relapsed Ewing sarcoma with respect to efficacy, toxicity and acceptability to patients.
Ethics approval
Not obtained at the time of registration
Study design
Multi-Arm, Multi-Stage (MAMS), randomised phase II/III, open-label multicentre international trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Paediatrics, Recurrent/refractory Ewing sarcoma
Intervention
At trial entry patients will be randomised to one of four chemotherapy regimens:
1. Topotecan and Cyclophosphamide (TC)
6 cycles of TC. Additional cycles may be given at the discretion of the treating clinician.
2. Irinotecan and Temozolomide (IT)
6 cycles of IT. Additional cycles may be given at the discretion of the treating clinician.
3. Gemcitabine and Docetaxel (GD)
6 cycles of GD. Additional cycles may be given at the discretion of the treating clinician.
4. High-dose Ifosfamide (IFOS)
4 cycles of IFOS.
Clinicians are encouraged to use local disease control measures where possible after four cycles of chemotherapy. Stem cell harvesting may be carried out in patients for whom high-dose therapy is planned but the first four chemotherapy cycles must be given according to the randomised regimen. Patients randomised to receive TC, IT or GD who have not progressed on treatment may continue to receive the randomised regimen for more than six cycles at the discretion of the treating physician. Myeloablative therapy may be given at the discretion of the treating physician after six cycles of TC, IT or GD, or after four cycles of IFOS.
Intervention type
Drug
Phase
Phase II/III
Drug names
Topotecan, cyclophosphamide, irinotecan, temozolomide, gemcitabine, docetaxel and ifosfamide (IFOS)
Primary outcome measure
Phase II: Objective Response Rate (ORR) will be measured by cross-sectional imaging according to RECIST criteria
Phase III: Progression-Free Survival (PFS) is defined as the time from randomisation until first event (progression, recurrence following response or death without progression or recurrence). Second malignancy is not classified as an event for progression-free survival. For those patients who do not experience event during the course of the trial, progression-free survival times will be censored at the date of their last available trial assessment.
Secondary outcome measures
1. Overall Survival (OS) is defined as the time from randomisation to death, irrespective of the cause. Surviving patients will be censored at their last follow-up date. OS will only be analysed for the first randomisation for each patient (re-randomisations will not be considered). Analysis methods will be as per PFS.
2. Adverse events and toxicity: Safety data will be summarised by arm for all treated patients using appropriate tabulations and descriptive statistics. Exploratory standard statistical tests will be performed to compare the arms.
3. Quality of Life (QoL) will be assessed at the following time points: baseline, following chemotherapy cycle 2, following chemotherapy cycle 4 using ≥18 years: EORTC QLQ-C30 , <18 years: PedsQL™ Generic Core Scales and Multidimensional Fatigue Score
4. Days spent in hospital while on trial treatment or due to trial treatment. The number (range) and proportion (with confidence intervals) of days in hospital will be presented for each arm and overall. Exploratory standard statistical tests will be performed to compare the arms.
Overall trial start date
31/03/2014
Overall trial end date
31/03/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed Ewing sarcoma
2. Disease recurrence after completion of first-line treatment
3. Refractory disease, defined by progression during first-line treatment or within 12 weeks of its completion
4. Soft tissue disease component evaluable by cross-sectional imaging. Patients with bone disease without a measurable soft tissue component or bone marrow disease only will be eligible for the study but will not contribute to the phase II primary outcome measure.
5. Age 2-50 years
6. Patient assessed as medically fit to receive cytotoxic chemotherapy
7. Documented negative pregnancy test for female patients of childbearing potential
8. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 5 months after last trial treatment (males), where applicable
9. Written informed consent from the patient and/or the parent/legal guardian
Participant type
Patient
Age group
Mixed
Gender
Both
Target number of participants
275 for phase II; 390 fpr phase III
Participant exclusion criteria
1. Conventional dose cytotoxic chemotherapy or other investigational medicinal product (IMP) within previous four weeks
2. Myeloablative dose chemotherapy within previous 8 weeks
3. Radiotherapy to target lesions within previous 6 weeks
4. Pregnant or breastfeeding women
5. Follow-up not possible due to social, geographic or psychological reasons
Additional criteria for specific arms:
1. Patients who have previously received one of the randomised regimens may not be randomised to receive that chemotherapy regimen again
2. Patients with a contraindication to any IMP may be entered into the study but may not be randomised to receive an arm that contains a contraindicated IMP
3. Patients who have received cyclophosphamide during first-line therapy may be randomised to receive the TC arm
4. Patients who have had ifosfamide during first-line therapy may be randomised to receive the IFOS arm if they do not have pre-existing renal or other toxicity that would necessitate a dose modification. There is no requirement for a minimum time between receiving first-line ifosfamide and randomisation to IFOS as part of the rEECur trial.
Recruitment start date
01/12/2014
Recruitment end date
30/09/2018
Locations
Countries of recruitment
France, Germany, Italy, Norway, Spain, United Kingdom
Trial participating centre
Christie Hospital
Manchester
M20 4BX
United Kingdom
Funders
Funder type
Government
Funder name
Seventh Framework Programme
Alternative name(s)
EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list