NCT01696669

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
43

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2010

Longer than P75 for phase_2

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 30, 2010

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

June 30, 2011

Completed
1.3 years until next milestone

First Posted

Study publicly available on registry

October 1, 2012

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 20, 2017

Completed
29 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 18, 2018

Completed
Last Updated

August 1, 2018

Status Verified

July 1, 2018

Enrollment Period

7.7 years

First QC Date

June 30, 2011

Last Update Submit

July 31, 2018

Conditions

Ewing's Sarcoma

Keywords

Ewing's SarcomaP6 protocol MSKCCGemcitabineDocetaxel

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival

    Assessment of the progression free survival in all the patients enrolled in the study 3 years after the completion of the treatment under study.

    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 (5)

  • Objective response rate (ORR)

    two months

  • Assessment of disease progression

    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.

    12 months

  • Assessment of bone marrow condition.

    24 months

  • Study the impact of patients treated with Cardioxane in cardioprotection

    6 months

Study Arms (1)

Chemotherapy + Surgery + Radiotherapy

EXPERIMENTAL

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. CHEMOTHERAPY: 1 cycle of vincristine-doxorubicin + dexrazoxane-cyclophosphamide, 1 cycle of ifosfamide-etoposide. 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.

Drug: ChemotherapyProcedure: SurgeryRadiation: Radiotherapy

Interventions

ChemotherapyDRUG

* Vincristine, 2 mg/m\^2 IV bolus, day 1. * Doxorubicin: 75 mg/m\^2 per cycle, or 25 mg/m\^2/day x 3 days, IV infusion, 1 hour (after dexrazoxane administration at the dose of 10:1). * Dexrazoxane: administered at a dose of 10:1, before doxorubicin only in adults. * Cyclophosphamide: 2100 mg/m\^2 IV infusion, 6 hours, with MESNA protection, days 1 and 2. * MESNA: used with cyclophosphamide and ifosfamide. The total daily dose of MESNA is equivalent to at least 60% of the daily dose of cyclophosphamide or ifosfamide. * G-CSF: 5 micrograms/kg/day SC. It starts 24 hours after the last dose of chemotherapy and continues until the absolute neutrophil count is ≥ 750 mm\^3/L. * Ifosfamide: 1800 mg/m\^2/day IV infusion, 1 hour, days 1-5 of each cycle (9,000 mg/m\^2 total maximum dose). Window phase in high-risk patients (21-days cycle): * Gemcitabine: 1000 mg/m\^2 IV, 90 minutes on day 1 and 8. * Docetaxel 100 mg/m\^2, 2-3 hour infusion on day 8.

Chemotherapy + Surgery + Radiotherapy
SurgeryPROCEDURE

Surgical intervention aiming to completely resect the tumor with negative margins.

Chemotherapy + Surgery + Radiotherapy
RadiotherapyRADIATION

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.

Chemotherapy + Surgery + Radiotherapy

Eligibility Criteria

AgeUp to 40 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, Spain

Location

Institut Català d'Oncologia l'Hospitalet

L'Hospitalet de Llobregat, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Son Espases

Palma de Mallorca, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Drug TherapySurgical Procedures, OperativeRadiotherapy

Condition Hierarchy (Ancestors)

OsteosarcomaNeoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsSarcoma

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

  • Jaume Mora Graupera, MD

    GEIS

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Jaume Mora

Study Record Dates

First Submitted

June 30, 2011

First Posted

October 1, 2012

Study Start

March 30, 2010

Primary Completion

December 20, 2017

Study Completion

January 18, 2018

Last Updated

August 1, 2018

Record last verified: 2018-07

Locations

ES(9)