Study of Intensive Chemotherapy, Surgery and Radiotherapy to Treat Ewing's Sarcoma in Children and Young Adults
Tumors of the Ewing sarcoma family (ES) affect children, adolescents and young adults. The reported incidence is 0.6 cases per million inhabitants every year. The peak incidence occurs between 10 and 20 years and it is rarely diagnosed beyond 30. The ES is a severe disease with a progression-free survival after 5 years of 60% in cases without metastasis and deadly in the majority of patients presenting metastasis. The ES is considered a systemic disease because, despite receiving an adequate local treatment, over 90% of patients deaths occur due to disseminated disease. Combined therapy of surgery, radiotherapy and chemotherapy has led to an improvement in the prognosis, achieving a survival of about 60% in most series
The MSKCC P6 protocol was developed for the treatment of high risk ES. In 2003, Kolb et al. reported the MSKCC experience after a 4-years follow-up of 68 patients who had been included from 1990 to 2001. Following the MSKCC P6 protocol, a survival rate of 82% was achieved in patients without metastasis, superior to the achieved with less intensive protocols. Following the guidelines of the MSKCC P6 protocol, in 2002 we modified the treatment schedule to create the modified P6 protocol (MP6). GEIS intends to develop MP6 as a clinical trial, which could provide the following potential advantages about current treatments:
- Lower total dose of alkylating agents.
- Early cardioprotection with dexrazoxane.
- Radiotherapy adjusted to the initial response.
- Pilot trial with the combination of Gemcitabine + Docetaxel for high-risk patients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2, Open-label, Uncontrolled, Multicenter and Prospective Study of Intensive Chemotherapy, Surgery and Radiotherapy to Treat Ewing's Sarcoma in Children and Young Adults|
- Progression Free Survival [ Time Frame: Assessment of the progression free survival in all the patients enrolled in the study 3 years after the completion of the treatment under study. ] [ Designated as safety issue: No ]Assessment of the progression free survival in all the patients enrolled in the study 3 years after the completion of the treatment under study.
- Objective response rate (ORR) [ Time Frame: two months ] [ Designated as safety issue: No ]To assess the objective response rate to treatment (ORR) defined following EMEA criteria (CPMP/EWP/205/95/Rev.3/Corr.2) in high risk patients with Ewing's sarcoma treated with an early window phase of Gemcitabine + docetaxel (G + D).
- Assessment of disease progression [ Time Frame: to reach an index of disease progression < 20% for high risk patients during the maintenance phase with Gemcitabine + Docetaxel. ] [ Designated as safety issue: No ]To assess the disease progression, aiming to reach an index of disease progression < 20% for high risk patients during the maintenance phase with Gemcitabine + Docetaxel.
- evaluate the toxicity and tolerance to the treatment Gemcitabine + Docetaxel in high risk patients, and toxicity and tolerance of mP6 treatment in all patients. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]To evaluate the toxicity and tolerance to the treatment Gemcitabine + Docetaxel in high risk patients, and toxicity and tolerance of mP6 treatment in all patients.
- Assessment of bone marrow condition. [ Time Frame: 24 months ] [ Designated as safety issue: No ]Molecular diagnosis and extension study of bone marrow in all patients included in the trial. Assessment of prognostic significance of the type of translocation and the molecular effect in the bone marrow.
- Study the impact of patients treated with Cardioxane in cardioprotection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]Creation of a cohort of patients treated with anthracyclines at high doses and early cardioprotection with dexrazoxane (Cardioxane). Long-term study of cardioprotection in these patients compared with historical series from the P6 protocol that did not received cardioprotection.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Chemotherapy + Surgery + Radiotherapy
Standard risk patients: MP6 Treatment:
CHEMOTHERAPY: 2 cycles of vincristine-doxorubicin + dexrazoxane-cyclophosphamide, 1 cycle of ifosfamide-etoposide. SURGERY: Ideally within 21 days after chemotherapy. RADIOTHERAPY: On the primary tumor bed in case of unresectable tumors, resected tumors with inadequate margins, or those with histologic response <90%.
High risk patients:
CHEMOTHERAPY: Window phase with 2 cycles of gemcitabine + docetaxel. MP6 TREATMENT. CHEMOTHERAPY: Maintenance therapy for 1 year with gemcitabine + docetaxel.
Window phase in high-risk patients (21-days cycle):
Surgical intervention aiming to completely resect the tumor with negative margins.Radiation: Radiotherapy
On the primary tumor bed in case of unresectable tumors, resected tumors with inadequate margins, or those with histologic response <90%. Patients will receive radiotherapy 21 days after the completion of chemotherapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01696669
|Contact: Jaume Mora Graupera, MD||+34 firstname.lastname@example.org|
|Hospital Clínic de Barcelona||Recruiting|
|Principal Investigator: Maurel, MD|
|Hospital de la Santa Creu i Sant Pau||Recruiting|
|Principal Investigator: López Pousa, MD|
|Hospital Vall d'Hebron||Recruiting|
|Principal Investigator: Valverde, MD|
|Hospital Sant Joan de Déu||Recruiting|
|Esplugues de Llobregat, Spain|
|Principal Investigator: Mora, Md|
|Institut Català d'Oncologia l'Hospitalet||Recruiting|
|Hospitalet de Llobregat, Spain|
|Principal Investigator: García del Muro, MD|
|Hospital Universitario de Canarias||Recruiting|
|La Laguna, Spain|
|Principal Investigator: Cruz, MD|
|Hospital Son Espases||Recruiting|
|Palma de Mallorca, Spain|
|Principal Investigator: Martín Broto, MD|
|Hospital Universitario Miguel Servet||Recruiting|
|Principal Investigator: Martínez Trufero, MD|
|Study Chair:||Jaume Mora Graupera, MD||GEIS|