Euro Ewing 2012 International randomized study for the treatment of newly diagnosed tumors of the Ewing sarcoma family
Descrizione riassuntiva dello studio
The aim of the Euro Ewing 2012 study is to compare different chemotherapies in terms of efficacy and side effects. The Euro-Ewing study 2012 is an international study. For all patients with Ewing sarcoma, the treatment includes both the administration of a combination of cancer drugs referred to as chemotherapy and surgical interventions and/or radiation therapy. The study is randomized in two ways. In a randomized study, patients are randomly assigned to different types of treatments (referred to as treatment groups). The assignment is done by a computer. This method means that neither the patient nor the doctor has any influence on which treatment group a study participant is assigned to. This ensures that the results are not biased in any way. In each treatment group, the same number of patients is treated. At the end of the study, the results are compared. When a patient is enrolled in the Euro-Ewing study 2012, they are randomly assigned to one of two different treatment groups: either Group A – the treatment method commonly used in Europe, or Group B – a chemotherapy commonly used in other countries. However, we do not know which treatment method is the best. This randomized study allows us to compare the two treatment methods.
(BASEC)
Intervento studiato
The treatment of an Ewing sarcoma includes 3 phases: 1) Induction therapy/
2) Local control - Surgery and/or radiation therapy/3) Consolidation phase.
Phase 1) Induction chemotherapy:
Group A:
6 cycles of VIDE chemotherapy administered at three-week intervals.
Group B:
9 cycles with VDC and IE. Patients receive alternating VDC and IE cycles. Nine cycles are administered at two-week intervals.
Phase 2):
After induction therapy, surgery and/or radiation therapy is performed, depending on where the tumor is located and how it responded to induction chemotherapy. Some tumors can be more easily operated on and removed than others. Tumors that can be surgically removed are examined under a microscope to determine how much of the tumor was killed by induction chemotherapy. If the tumor is located in a part of the body where it cannot be surgically removed, it will be treated with radiation therapy.
Phase 3): Consolidation chemotherapy.
The form of consolidation therapy depends on the size of the tumor, the patient's response to induction therapy, and whether the tumor has spread to other parts of the body.
Group A:
If the tumor is small and/or has responded well to induction therapy, patients receive: 1 cycle of VAI chemotherapy, followed by 7 cycles of VAC chemotherapy. VAI and VAC cycles are administered at three-week intervals. If the tumor is larger and/or has responded less well to induction therapy, patients receive: 1 cycle of VAI chemotherapy, followed by high-dose chemotherapy (BuMel). High-dose BuMel chemotherapy is administered for five days via a central venous catheter. For patients receiving such high-dose treatment, an autologous stem cell transplant is also performed. Stem cells, which were obtained from the blood during the first treatment phase, are reintroduced into the body the day after treatment ends via the central venous catheter to reduce the side effects of chemotherapy. Radiation therapy may also be used. If the tumor has spread to other parts of the body, patients receive 8 cycles of VAI chemotherapy plus radiation therapy. VAI cycles are administered at three-week intervals.
Group B:
If the tumor is larger and/or has responded less well to induction therapy, patients receive the following standard therapy: 1 cycle of VAI chemotherapy, followed by high-dose BuMel chemotherapy. If the tumor is small and/or has responded well to induction therapy, or has spread to other parts of the body, patients receive: five alternating cycles with IE and VC: five cycles are administered at two-week intervals.
If the tumor has metastasized, patients also receive radiation therapy.
Groups A and B:
During treatment, routine examinations are performed to monitor progress. After each cycle of chemotherapy, blood tests and a physical examination are performed. Imaging procedures (CT or MRI) and echocardiograms are performed as needed.
After the treatment is completed, the study team will continue to collect information about your health status for at least 5 years. For this purpose, you will come to regular appointments at the clinic so that this information can be collected.
(BASEC)
Malattie studiate
newly diagnosed tumors of the Ewing sarcoma family
(BASEC)
Histologically and genetically confirmed Ewing sarcoma of bone or soft tissue Age: 18 to 50 No previous treatment for Ewing's sarcoma except surgery (BASEC)
Criteri di esclusione
Contraindications to treatment Second malignancy Pregnant or breastfeeding women (BASEC)
Luogo dello studio
Berna, San Gallo, Zurigo
(BASEC)
Sponsor
University of Birmingham, GB-Birmingham Swiss Cancer Institute, CH-Bern
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Krista Zackel
+41 31 389 91 91
trials@clutterswisscancerinstitute.chSwiss Cancer Institute
(BASEC)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Berna
(BASEC)
Data di approvazione del comitato etico
24.07.2018
(BASEC)
ID di studio ICTRP
EUCTR2012-002107-17 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours. (BASEC)
Titolo accademico
International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours - Euro Ewing 2012 (ICTRP)
Titolo pubblico
International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours (ICTRP)
Malattie studiate
Ewing's Sarcoma Family of Tumours
MedDRA version: 20.0Level: PTClassification code 10015560Term: Ewing's sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)
Intervento studiato
Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-
Product Name: Doxorubicin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Doxorubicin
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
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Product Name: Vincristine
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
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
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-
Product Name: Actinomycin D
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Dactinomycin
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-
Product Name: Zoledronic Acid
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Zoledronic acid
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 0.04 0.8-
Trade Name: Busilvex
Product Name: Busilvex
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: BUSULFAN
Current Sponsor code: C6 H14 O6 S2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-
Trade Name: Melphalan
Product Name: Melphala (ICTRP)
Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)
Disegno dello studio
Controlled: yesRandomised: yesOpen: yesSingle blind: noDouble blind: noParallel group: noCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: yesPlacebo: noOther: noNumber of treatment arms in the trial: 6 (ICTRP)
Criteri di inclusione/esclusione
Inclusion criteria:
• Any histologically and genetically confirmed ESFT of bone or soft tissue, or round cell sarcomas 'Ewing's-like'
but which are negative for EWSR1 gene rearrangement.
• 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
(ICTRP)
Exclusion criteria:
• 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
Endpoint primari e secondari
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/BuMel 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.;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);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. (ICTRP)
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: • Overall Survival (OS)- evaluated continually
• Adverse events and toxicity – evaluated after each course of chemotherapy, or as reported
• Histological response if surgery is performed – evaluated at the time of surgery following induction chemotherapy
• Response of primary tumour, regional lymph nodes and/or metastases - evaluated after cycle 2 or 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/ear osteonecrosis (R2 only)– evaluated during or at end of treatment (ICTRP)
Data di registrazione
10.08.2015 (ICTRP)
Inclusione del primo partecipante
07.08.2015 (ICTRP)
Sponsor secondari
non disponibile
Contatti aggiuntivi
Jennifer Anderton, ee2012@trials.bham.co.uk, 00441214159877, University of Birmingham (ICTRP)
ID secondari
RG_11-152, ISRCTN92192408, 2012-002107-17-GB (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002107-17 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours (ICTRP)
Link ai risultati nel registro primario
non disponibile