Clinical trial for the treatment of Ewing sarcoma

Conditions

Ewing sarcoma Malignant peripheral neuroectodermal tumour Askin tumour Atypical Ewing sarcoma MedDRA version: 20.1 Level: PT Classification code 10057846 Term: Primitive neuroectodermal tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10057656 Term: Askin's tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0

Raphael Koch, Lianne Haveman, Ruth Ladenstein, Bénédicte Brichard, Heribert Jürgens et al. (42 authors)

Clinical Cancer Research2023-10-169 citations

10.1158/1078-0432.ccr-23-1966

Efficacy of maintenance therapy with zoledronic acid in patients with localized Ewing sarcoma: Report from the international Ewing 2008 trial.

Uta Dirksen, Raphael Koch, Vivek A. Bhadri, Bénédicte Brichard, Trude Butterfaß‐Bahloul et al. (21 authors)

Journal of Clinical Oncology2020-05-2012 citations

10.1200/jco.2020.38.15_suppl.11523

Efficacy of add-on treosulfan and melphalan high-dose therapy in patients with high-risk metastatic Ewing sarcoma: Report from the International Ewing 2008R3 trial.

Uta Dirksen, Vivek A. Bhadri, Bénédicte Brichard, Trude Butterfaß‐Bahloul, Soňa Cyprová et al. (21 authors)

Journal of Clinical Oncology2020-05-208 citations

10.1200/jco.2020.38.15_suppl.11501

Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

van den Berg H, Paulussen M, Le Teuff G, Judson I, Gelderblom H, Dirksen U, Brennan B, Whelan J, Ladenstein RL, Marec-Berard P, Kruseova J, Hjorth L, Kühne T, Brichard B, Wheatley K, Craft A, Juergens H, Gaspar N, Le Deley MC, Euro-EWING99 Group.

2015-08-1014 citations

10.1016/j.ejca.2015.06.123

Interventions

Trade Name: Zometa Product Name: Zometa Product Code: not applicable Pharmaceutical Form: Concentrate for solution for injection INN or Proposed INN: not applicable CAS Number: 165800-06-6 Current Sp

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Histologically confirmed Ewing tumour of bone or soft tissue. - Either sex, age >48 months (for GPOH patients) and 50%, may be modified for handicapped patients. - Haemoglobin > 8 g/dl, Platelets > 80.000/µl, WBC > 2000/µl. - LVSF > 40%, FS >28%. Are the trial subjects under 18? yes Number of subjects for this age range: 1021 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - More than one cycle of chemotherapy prior to registration - Second malignancy - Pregnancy and lactation - Any other medical, psychiatric, or social condition incompatible with the protocol treatment

Design outcomes

Primary

Measure	Time frame
Main Objective: Randomised trial to test for superiority regarding event-free survival (EFS) Standard Risk R1: in localised Ewing tumour (ET) with good histological response or initial tumour volume 200ml (R2loc): busulfan/melphalan high dose chemotherapy (HDT) and autologous stem cell reinfusion versus standard chemotherapy . In pulmonary metastases: busulfan/melphalan HDT and autologous stem cell reinfusion (SCT) versus standard chemotherapy plus whole lung irradiation (R2pulm). Very High Risk R3: in primary disseminated disease: treosulfan-melphalan HDT and autologous SCT add-on to 8 cycles of standard adjuvant chemotherapy versus 8 cycles of standard adjuvant chemotherapy alone. ;Secondary Objective: - To investigate whether any of the following improves overall survival: in R1: add-on fenretinide, bisphosphonates or bisphosphonates + fenretinide compared to no add-on treatment. in R2: high dose chemotherapy with busulfan/melphalan. in R3: high dose chemotherapy with treosulfan-melphalan. - To evaluate short and long-term toxicity. - To analyse the overall outcome. - To analyse quality of life overall and regarding impact of add-on treatment. - To examine the value of PET for diagnosis. - To investigate the impact of time to diagnosis. ;Primary end point(s): Event-free survival (The principal coordinating investigator is responsible for regular follow-up for all patients. The trial offices on behalf of the principal investigator are responsible for at least one yearly update on events in each single patient) ;Timepoint(s) of evaluation of this end point: For all risk groups R1, R2loc,R2pulm and R3 three interim analyses are intended to be performed using an inverse normal design corresponding to an equally spaced four step group sequential design according to O’Brien & Fleming (Wassmer 2006, O’Brien & Fleming 1979). After each interim analysis a data dependent sample size calculation may be performed. Then, the accrual period, the observation time and the sch	—

Measure

Time frame

Main Objective: Randomised trial to test for superiority regarding event-free survival (EFS) Standard Risk R1: in localised Ewing tumour (ET) with good histological response or initial tumour volume 200ml (R2loc): busulfan/melphalan high dose chemotherapy (HDT) and autologous stem cell reinfusion versus standard chemotherapy . In pulmonary metastases: busulfan/melphalan HDT and autologous stem cell reinfusion (SCT) versus standard chemotherapy plus whole lung irradiation (R2pulm). Very High Risk R3: in primary disseminated disease: treosulfan-melphalan HDT and autologous SCT add-on to 8 cycles of standard adjuvant chemotherapy versus 8 cycles of standard adjuvant chemotherapy alone. ;Secondary Objective: - To investigate whether any of the following improves overall survival: in R1: add-on fenretinide, bisphosphonates or bisphosphonates + fenretinide compared to no add-on treatment. in R2: high dose chemotherapy with busulfan/melphalan. in R3: high dose chemotherapy with treosulfan-melphalan. - To evaluate short and long-term toxicity. - To analyse the overall outcome. - To analyse quality of life overall and regarding impact of add-on treatment. - To examine the value of PET for diagnosis. - To investigate the impact of time to diagnosis. ;Primary end point(s): Event-free survival (The principal coordinating investigator is responsible for regular follow-up for all patients. The trial offices on behalf of the principal investigator are responsible for at least one yearly update on events in each single patient) ;Timepoint(s) of evaluation of this end point: For all risk groups R1, R2loc,R2pulm and R3 three interim analyses are intended to be performed using an inverse normal design corresponding to an equally spaced four step group sequential design according to O’Brien & Fleming (Wassmer 2006, O’Brien & Fleming 1979). After each interim analysis a data dependent sample size calculation may be performed. Then, the accrual period, the observation time and the sch

—

Secondary

Measure	Time frame
Secondary end point(s): 1) Overall survival 2) Toxicity 3) Outcome 4) Quality of life 5) Value of Positron Emission Tomography 6) Relevance of time to diagnosis;Timepoint(s) of evaluation of this end point: 1), 3), 4), 5), 6) 2 years from end of accrual 2) about 3 months from end of last study patient's treatment	—

Countries

Australia, Austria, Belgium, Czech Republic, Finland, Germany, Hungary, Lithuania, Netherlands, New Zealand, Poland, Sweden, Switzerland

Contacts

Public ContactEWING 2008 Trial Office

Universitaetsklinikum Münster, Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie

ewing@uk-essen.de492017238082

Outcome results

None listed