First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years (CombinaiR3)

Summary

Ewing's 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 mg/m²) and Melphalan (140 mg/m²), 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 3.9 years after diagnosis, and a median survival time of 1.6 years.

Conditions

• Ewing Sarcoma Family of Tumors

Interventions

DRUG

VDC-IE x2

Week 1, 5, 9 and week 13: * Vincristine, IV, D1, 1.5mg/m² * Doxorubicine, IV, D1-D2, 37.5mg/m² * Cyclophosphamide, IV, D1, 1.2g/m² Week 3, 7, 11 and week 15: * Ifosfamide, IV, D15 to D19, 1.8g/m²/d * Etoposide, IV, D15 to D19, 100mg/m²/d

DRUG

VDC-IE

Week 1 and week 5: * Vincristine, IV, D1, 1.5mg/m² * Doxorubicine, IV, D1-D2, 37.5mg/m² * Cyclophosphamide, IV, D1, 1.2g/m² Week 3, and week 7: * Ifosfamide, IV, D15 to D19, 1.8g/m²/d * Etoposide, IV, D15 to D19, 100mg/m²/d

DRUG

TEMIRI

Week 9, 12, 15 and week 18: * Temozolomide, PO, D1 to D5, 150mg/m²/d * Irinotecan, IV, D1 to D5, 50mg/m²/d

DRUG

Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC: * Busulfan, IV, D-5 to D-2, dosa according to the weight * Melphalan, IV, D-1, 140 mg/m² Peripheral Blood Stem Cell infusion: \- PBSC infusion, D0, at least 3.10\^6 CD34/kg

DRUG

Maintenance

\* 1st year : VC * Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week) * Cyclophosphamide, PO, 25mg/m² continuously

PROCEDURE

Local treatment by surgery

Surgical excision of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy. Radiotherapy can be added

RADIATION

Local treatment by radiotherapy

Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy

Sponsors & Collaborators

• UNICANCER

  collaborator OTHER

• Institut Curie

  lead OTHER

Principal Investigators

• Valérie LAURENCE, MD · Institut Curie

• Nadège CORRADINI, MD · Institut d'Hématologie et d'Oncologie Pédiatrique

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-12-31

Primary Completion

2022-08-31

Completion

2023-11-30

Countries

• France

Study Locations