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SNCTP000002777 | ISRCTN36453794 | BASEC2017-02134

Internationale, randomisierte klinische Studie für Patienten mit rezidiviertem oder nicht auf die Standardbehandlung ansprechendem Ewing-Sarkom

Data source: BASEC (Imported from 08.11.2024), WHO (Imported from 07.11.2024)
Changed: Aug 22, 2024, 2:59 PM
Disease category: Other Cancer

Brief description of trial (Data source: BASEC)

Es handelt sich bei rEECur um eine internationale Studie, welche durch die University of Birmingham in Grossbritannien als Sponsor veranlasst wird. Es können Patientinnen und Patienten aus ganz Europa, sowie aus Australien und Neuseeland teilnehmen. Für die Durchführung der Studie in der Schweiz übernimmt die Schweizerische Pädiatrische Onkologie Gruppe (SPOG) die Verantwortung. Bis heute gibt es keine Standardtherapie für Ewing-Sarkom Patientinnen und Patienten, bei denen die bisherige Behandlung nicht anspricht oder für Patientinnen und Patienten welche ein Rezidiv des Ewing-Sarkoms erleiden. Momentan entscheiden die Ärztinnen und Ärzte anhand von bestimmten Faktoren, welche Behandlung (z. B. Chemotherapie, Operation und/oder Strahlentherapie) in welcher Situation zu wählen ist. Alle Chemotherapien sind wirksam, aber man weiss nicht, welche sich am besten eignet. Im Rahmen der rEECur-Studie werden unterschiedliche Chemotherapien mit etablierten Medikamenten miteinander vergleichen. Patientinnen und Patienten welche an der Studie teilnehmen, werden durch ein Computerprogramm nach dem Zufallsprinzip (Randomisierung) einer der Therapiegruppen zugeteilt. Die Resultate der verschiedenen Therapien werden laufend analysiert. Im Verlauf der Studie können Therapien, welchen weniger gut funktionieren, aus der Studie entfernt werden. Es können auch neue Therapien dazukommen.

Health conditions investigated(Data source: BASEC)

Diese Studie untersucht das Ewing-Sarkom - ein seltener, bösartiger und meist knochenassoziierter Tumor.

Health conditions (Data source: WHO)

Paediatrics, Recurrent/refractory Ewing sarcoma
Cancer

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Die Patientinnen und Patienten werden zufällig einer der geeigneten Therapiegruppen (sog. Therapiearmen) zugeteilt. Jede Gruppe erhält eine andere Art von Chemotherapie. Diese umfasst die Verabreichung von einem oder mehreren Medikamenten. Momentan sind zwei Therapiearme für die Rekrutierung geöffnet. Die Therapiearme heissen IFOS (Ifosfamid) und IFOS-L (Ifosfamid/Lenvatinib). Vier Therapiearme sind inzwischen aus der Studie ausgeschlossen worden. Dies nachdem Zwischenanalysen gezeigt haben, dass diese Arme weniger gut funktionierten als die übrigen Arme. Zudem kam kürzlich ein neuer Therapiearm dazu.
Vor dem Start der Studie werden möglicherweise übliche Untersuchungen wie Analyse von Blut- und Urinproben, klinische Untersuchungen, Herzuntersuchungen sowie bildgebende Untersuchungen durchgeführt. Darüber hinaus wird das Knochenmark untersucht und gegebenenfalls eine Biopsie des Rezidivtumors durchgeführt. Während der Behandlung werden die Patientinnen und Patienten, den Standards der Behandlung entsprechend, regelmässig untersucht. Nach 4 Kursen Chemotherapie erhalten die Patientinnen und Patienten eine erneute Bildgebung um festzustellen, ob der Tumor gut auf die Behandlung angesprochen hat. Am Ende der Behandlung werden die Patientinnen und Patienten vollständig untersucht und es werden nochmals bildgebende Untersuchungen des Tumors durchgeführt.
Mit kurzen Befragungen vor und während der Behandlung wollen wir ausserdem etwas über die Lebensqualität der Patientinnen und Patienten erfahren. Nach Therapieende möchte die Studienleitung fünf Jahre lang Informationen über den Gesundheitszustand der Patientinnen und Patienten sammeln. Dies geschieht bei den üblicherweise geplanten Nachsorgeuntersuchungen.

Interventions (Data source: WHO)

At trial entry patients will be randomised to one of four chemotherapy regimens:
1. Topotecan and cyclophosphamide (TC): 6 cycles. Additional cycles may be given at the discretion of the treating clinician.
2. Irinotecan and temozolomide (IT): 6 cycles. Additional cycles may be given at the discretion of the treating clinician.
3. Gemcitabine and docetaxel (GD): 6 cycles. Additional cycles may be given at the discretion of the treating clinician.
4. High-dose Ifosfamide (IFOS): 4 cycles.

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.

Criteria for participation in trial (Data source: BASEC)

- Rezidiviertes oder nicht auf die Standardbehandlung ansprechendes Ewing-Sarkom
- Fortschreitender Krankheitsveraluf (während oder nach Beendung der first line Therapie)
- cytotoxische Chemotherapie durchführbar
- Alter ab 2 Jahren

Exclusion criteria (Data source: BASEC)

- Behandlung mittels Bestrahlung während der letzten 6 Wochen
- Cytotoxische Chemotherapie oder andere Therapie mittels investigativen medizinischen Produkten (IMP) während der letzten 2 Wochen
- vorgängiger Einschluss in die rEECur Studie

Inclusion/Exclusion Criteria (Data source: WHO)

Gender: Both
Inclusion criteria: Participant inclusion criteria as of 14/12/2018:
1. Histologically confirmed ES.
2. Disease progression (during or after completion of first line treatment) or any subsequent recurrence OR Refractory disease, defined by progression during first line treatment or within 12 weeks of its completion. Disease progression will be based on RECIST criteria. The appearance of new bone lesions on bone scan will require confirmation with cross-sectional imaging.
3. Soft tissue disease component evaluable by cross-sectional imaging (RECIST). 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.
4. Age =4 years and <50 years.
5. Patient assessed as medically fit to receive cytotoxic chemotherapy.
6. Documented negative pregnancy test for female patients of childbearing potential.
7. Patient agrees to use effective contraception during therapy and for 12 months after last trial treatment, where applicable.
8. Written informed consent from the patient and/or parent/legal guardian.

Previous 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
Exclusion criteria: Participant exclusion criteria as of 14/12/2018:
1. Bone marrow infiltration resulting in Absolute Neutrophil Count (ANC) <1.0 x 109/L or platelets <75 x 109/L.
2. Cytotoxic chemotherapy or other investigational medicinal product (IMP) within previous two weeks.
3. Myeloablative therapy within previous eight weeks.
4. Radiotherapy to target lesion within previous six weeks.
5. Pregnant or breastfeeding women.
6. Follow-up not possible due to social, geographic or psychological reasons.
7. Previous randomisation into the rEECur trial

Additional criteria for specific arms:
1. 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. They will be eligible for trial entry as long as they can be randomised between a minimum of two study arms.
2. Patients who are unable to receive one or more IMPs due to local or national funding arrangements will be eligible for trial entry as long as they can be randomised between a minimum of two study arms.
3. Patients and investigators may decline randomisation to one or more trial regimens but will be eligible for trial entry as long as they can be randomised between a minimum of two study arms.
4. Patients who have previously received one of the trial regimens off-trial may not be randomised to receive that chemotherapy regimen again. However, patients who have received cyclophosphamide during first line therapy may be randomised to receive the TC arm and patients who have had ifosfamide during first line therapy may receive the ifosfamide arm if they do not have pre-existing renal or other toxicity that would necessitate in rEECur a dose modification. There is no requirement for a minimum time between receiving first line ifosfamide and entry to rEECur.


Previous 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.

Further information on the trial in WHO primary registry

https://www.isrctn.com/ISRCTN36453794

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN36453794
Further information on trial

Date trial registered

Feb 14, 2014

Incorporation of the first participant

Dec 1, 2014

Recruitment status

Ongoing

Academic title (Data source: WHO)

rEECur: an international randomised controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Multi-Arm, Multi-Stage (MAMS), randomised phase II/III, open-label multicentre international trial (Treatment)

Phase (Data source: WHO)

Phase II/III

Primary end point (Data source: WHO)

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.

Secundary end point (Data source: WHO)

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.

Contact information (Data source: WHO)

Seventh Framework Programme

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

Not expected to be made available
Planned publication in a high-impact peer-reviewed journal with intention of publishing one year post planned interim analyses.

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Aarau, Basel, Bellinzona, Bern, Geneva, Lausanne, Luzern, St. Gallen, Zurich

Countries (Data source: WHO)

Australia, Belgium, Czech Republic, Denmark, England, Finland, France, Germany, Hungary, Italy, Netherlands, New Zealand, Northern Ireland, Norway, Poland, Scotland, Spain, Sweden, Switzerland, United Kingdom, Wales

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Dr. med. Willemijn Breunis
+41 44 266 74 55
willemijn.breunis@kispi.uzh.ch

Contact for scientific information (Data source: WHO)

Martin
McCabe
rEECur Trial OfficeCancer Research UK Clinical Trials Unit (CRCTU)Institute of Cancer and Genomic SciencesUniversity of BirminghamEdgbaston
+44 (0) 121 415 9877
reecur@trials.bham.ac.uk

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Date of authorisation by the ethics committee

20.02.2018

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2017-02134

Secondary ID (Data source: WHO)

2014-000259-99
vn 5.0 vd 03-Jun-2016
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