Ignite Creation Date:
2024-05-06 @ 9:34 AM
Last Modification Date:
2024-10-26 @ 12:16 PM
Study NCT ID:
NCT03011528
Status:
COMPLETED
Last Update Posted:
2024-01-29
First Post:
2016-12-06
Brief Title:
First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years
Sponsor:
Institut Curie
Organization:
Institut Curie
Study Overview
Official Title:
CombinaiR3 - First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years
Status:
COMPLETED
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CombinaiR3
Brief Summary:
Ewings sarcoma and related tumours ESFT are rare tumours with a peak incidence in the second decade of life They start most often from bone and are characterized by a specific translocation involving the so-called EWS gene In one patient out of three the staging procedures detect metastatic tumours at the diagnosis most commonly in lungs bones and bone marrow
ESFT treatment strategy is multidisciplinary combining primary chemotherapy a local treatment and consolidation chemotherapy
The primary metastatic dissemination is the most important prognostic factor as the survival rate is around 70-75 for localized tumours in contrast with less than 50 for patients with primary metastatic disease
Among primary metastatic patients bone involvement and or bone marrow strike markedly the prognosis of these patients While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50 whereas it is only from 0 to 25 in patients with bone marrow involvement
In 1999 the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours For the patients with primary extrapulmonary metastatic Ewing tumours R3 patients the protocol proposed a heavy induction chemotherapy in order to propose a consolidation with high dose chemotherapy to a higher rate of patients The high-dose Busulfan Melphalan chemotherapy BuMel was based on Busulfan 600 mgm² and Melphalan 140 mgm² with autologous peripheral blood stem cell PBSC support
Of note for the full population of patients with metastatic disease the 3-year EFS rate was 27 SD 3 and the OS rate was 34 SD 4 with a median follow-up of 39 years after diagnosis and a median survival time of 16 years
ESFT treatment strategy is multidisciplinary combining primary chemotherapy a local treatment and consolidation chemotherapy
The primary metastatic dissemination is the most important prognostic factor as the survival rate is around 70-75 for localized tumours in contrast with less than 50 for patients with primary metastatic disease
Among primary metastatic patients bone involvement and or bone marrow strike markedly the prognosis of these patients While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50 whereas it is only from 0 to 25 in patients with bone marrow involvement
In 1999 the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours For the patients with primary extrapulmonary metastatic Ewing tumours R3 patients the protocol proposed a heavy induction chemotherapy in order to propose a consolidation with high dose chemotherapy to a higher rate of patients The high-dose Busulfan Melphalan chemotherapy BuMel was based on Busulfan 600 mgm² and Melphalan 140 mgm² with autologous peripheral blood stem cell PBSC support
Of note for the full population of patients with metastatic disease the 3-year EFS rate was 27 SD 3 and the OS rate was 34 SD 4 with a median follow-up of 39 years after diagnosis and a median survival time of 16 years
Detailed Description:
Ewings sarcoma and related tumours ESFT are rare tumours with a peak incidence in the second decade of life They start most often from bone and are characterized by a specific translocation involving the so-called EWS gene The gene rearrangement results in the production of a transcription factor in the majority EWS-FLI1 transcription
In one patient out of three the staging procedures detect metastatic tumours at the diagnosis metastases involve most commonly lungs bones and bone marrow
Therefore in addition to local imaging the initial extension assessment of any Ewing tumour includes at least a chest CT scan and a bone marrow extensive evaluation comprising bone marrow punctures into several different sectors bone marrow biopsies and a bone imaging evaluation The FDG-PET scan is more sensible than bone scan and conventional imaging as MRI in detection of bone metastases It is more and more widely used in the bone metastasis search in Ewing tumours and seems useful to complement the search of extra-osseous metastases outside the lungs including that of bone marrow metastases The full-body MRI is still under evaluation for the disease extension evaluation
ESFT treatment strategy is multidisciplinary combining primary chemotherapy a local treatment and consolidation chemotherapy The local treatment may combine surgery and or radiotherapy according to the tumour site and size and to the tumour response ESFT chemotherapy is based on alkylating agents ifosfamide and or cyclophosphamide etoposide anthracyclines vincristine and actinomycin
The primary metastatic dissemination is the most important prognostic factor as the survival rate is around 70-75 for localized tumours in contrast with less than 50 for patients with primary metastatic disease Among primary metastatic patients bone involvement and or bone marrow strike markedly the prognosis of these patients While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50 whereas it is only from 0 to 25 in patients with bone marrow involvement
In 1999 the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours localized or metastatic and below 50 years of age For the patients with primary extrapulmonary metastatic Ewing tumours R3 patients the protocol proposed a heavy induction chemotherapy in order to propose a consolidation with high dose chemotherapy to a higher rate of patients The high-dose BuMel chemotherapy was based on Busulfan 600 mgm² and Melphalan 140 mgm² with autologous peripheral blood stem cell PBSC support
The study enrolled 281 patients with primary dissemination and skeletal metastases with or without bone marrow involvement and with or without additional pulmonary metastases or metastases to other sites In contrast to the distribution in the entire group of patients with Ewing tumours the primary site in this subgroup was extremity in only 31 patients pelvisabdomen in 45 and axialother in 24 patients The overall survival at 3 years was 28 SD 4 in the group with primary tumour in the abdomen or pelvis versus 39 SD 6 for each of the two other groups Of note for the full population of patients with metastatic disease the 3-year EFS rate was 27 SD 3 and the OS rate was 34 SD 4 with a median follow-up of 39 years after diagnosis and a median survival time of 16 years
In one patient out of three the staging procedures detect metastatic tumours at the diagnosis metastases involve most commonly lungs bones and bone marrow
Therefore in addition to local imaging the initial extension assessment of any Ewing tumour includes at least a chest CT scan and a bone marrow extensive evaluation comprising bone marrow punctures into several different sectors bone marrow biopsies and a bone imaging evaluation The FDG-PET scan is more sensible than bone scan and conventional imaging as MRI in detection of bone metastases It is more and more widely used in the bone metastasis search in Ewing tumours and seems useful to complement the search of extra-osseous metastases outside the lungs including that of bone marrow metastases The full-body MRI is still under evaluation for the disease extension evaluation
ESFT treatment strategy is multidisciplinary combining primary chemotherapy a local treatment and consolidation chemotherapy The local treatment may combine surgery and or radiotherapy according to the tumour site and size and to the tumour response ESFT chemotherapy is based on alkylating agents ifosfamide and or cyclophosphamide etoposide anthracyclines vincristine and actinomycin
The primary metastatic dissemination is the most important prognostic factor as the survival rate is around 70-75 for localized tumours in contrast with less than 50 for patients with primary metastatic disease Among primary metastatic patients bone involvement and or bone marrow strike markedly the prognosis of these patients While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50 whereas it is only from 0 to 25 in patients with bone marrow involvement
In 1999 the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours localized or metastatic and below 50 years of age For the patients with primary extrapulmonary metastatic Ewing tumours R3 patients the protocol proposed a heavy induction chemotherapy in order to propose a consolidation with high dose chemotherapy to a higher rate of patients The high-dose BuMel chemotherapy was based on Busulfan 600 mgm² and Melphalan 140 mgm² with autologous peripheral blood stem cell PBSC support
The study enrolled 281 patients with primary dissemination and skeletal metastases with or without bone marrow involvement and with or without additional pulmonary metastases or metastases to other sites In contrast to the distribution in the entire group of patients with Ewing tumours the primary site in this subgroup was extremity in only 31 patients pelvisabdomen in 45 and axialother in 24 patients The overall survival at 3 years was 28 SD 4 in the group with primary tumour in the abdomen or pelvis versus 39 SD 6 for each of the two other groups Of note for the full population of patients with metastatic disease the 3-year EFS rate was 27 SD 3 and the OS rate was 34 SD 4 with a median follow-up of 39 years after diagnosis and a median survival time of 16 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None