Clinical trial NCT01696669: Study of Intensive Chemotherapy, Surgery and Radiotherapy to Treat Ewing's Sarcoma in Children and Young Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ewing's Sarcoma
Keywords: Ewing's Sarcoma
P6 protocol MSKCC
Gemcitabine
Docetaxel
Lead sponsor: Grupo Espanol de Investigacion en Sarcomas
Sponsor class: OTHER
First posted: 2012-10-01
Enrollment: 43
Sex: ALL
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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:

1. Lower total dose of alkylating agents.
2. Early cardioprotection with dexrazoxane.
3. Radiotherapy adjusted to the initial response.
4. Pilot trial with the combination of Gemcitabine + Docetaxel for high-risk patients.


Eligibility criteria: Inclusion Criteria:

* Patients with Ewing's Sarcoma in which the molecular analysis has been performed in one of the 2 reference laboratories of the study and the EWS gene rearrangement has been confirmed by RT-PCR in the Hospital Sant Joan de Déu de Barcelona, or by fluorescence in situ hybridization (FISH) in the Cancer Research Center of Salamanca.
* High-risk patients will be those patients with metastases, patients with primary tumor in pelvis or axial bones and patients with (micro) metastases in bone marrow detected by the molecular study. The remaining patients will be considered as standard risk. Lung nodules identified by CT-scan with diameter \> 5 mm will be considered metastatic. Nodules ≤ 5 mm will be biopsied.
* Age ≤ 40 years.
* Adequate renal and hepatic function , defined as calculated creatinine clearance \> 60 ml/min, creatinine, total bilirubin, AST and/or ALT \< 1,5 times the upper limit of normal (ULN).
* Normal cardiac function defined by echocardiography, or ejection fraction ≥ 55%.
* ECOG performance status 0 - 1 (Appendix VIII).
* Informed consent form signed by parents, guardians or the patient (if over 18 years), prior to the start of treatment.
* Patients of childbearing age (both men and women) must use effective contraceptive methods before study entry and during the realization of it. Effective contraceptive methods for both women and men should be extended to 6 months after stopping the treatment under study. Pregnancy must be excluded by urine test (negative pregnancy test) prior to the inclusion in the study.

Exclusion Criteria:

* Pregnancy or breastfeeding.
* Active infection or other severe concomitant diseases.
* Severe psychiatric conditions that make impossible to obtain the signed informed consent form or limit the treatment compliance.
* Concurrent treatment with other experimental drugs within 30 days prior to study entry.
* History of previous cancer diagnosed or treated in the past 5 years except basal cell carcinoma, cervical carcinoma in situ or superficial bladder cancer.

Primary outcomes:
measure: Progression Free Survival
timeFrame: Assessment of the progression free survival in all the patients enrolled in the study 3 years after the completion of the treatment under study.
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: two months
measure: Assessment of disease progression
timeFrame: to reach an index of disease progression < 20% for high risk patients during the maintenance phase with Gemcitabine + Docetaxel.
measure: evaluate the toxicity and tolerance to the treatment Gemcitabine + Docetaxel in high risk patients, and toxicity and tolerance of mP6 treatment in all patients.
timeFrame: 12 months
measure: Assessment of bone marrow condition.
timeFrame: 24 months
measure: Study the impact of patients treated with Cardioxane in cardioprotection
timeFrame: 6 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
city: Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia l'Hospitalet
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: GEIS
name: Jaume Mora Graupera, MD
role: STUDY_CHAIR
References: