Ewing's SarcomaPhase 2NCT01696669
Study of Intensive Chemotherapy, Surgery and Radiotherapy to Treat Ewing's Sarcoma in Children and Young Adults
A Phase 2 study testing Chemotherapy, Surgery and Radiotherapy in people with Ewing's Sarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 9 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 40 years
- Conditions the study is for
- Ewing's Sarcoma
- What is being tested?
- Chemotherapy, Surgery and Radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 9 sitesSpain
- Study dates
- 30 Mar 2010to 18 Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Spain9 sites
Hospital Clínic de Barcelona
Barcelona
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Vall d'Hebron
Barcelona
Hospital Sant Joan de Déu
Esplugues de Llobregat
Institut Català d'Oncologia l'Hospitalet
L'Hospitalet de Llobregat
Hospital Ramón y Cajal
Madrid, 28034
Hospital Son Espases
Palma de Mallorca
Hospital Universitario de Canarias
San Cristóbal de La Laguna
Hospital Universitario Miguel Servet
Zaragoza
About this study
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
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.
- Conditions
- Ewing's Sarcoma
- Being tested
- Chemotherapy, Surgery, Radiotherapy
- Keywords
- Ewing's Sarcoma, P6 protocol MSKCC, Gemcitabine, Docetaxel
- Medical subject headings
- Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
SurgeryProcedure or surgery
Surgical intervention aiming to completely resect the tumor with negative margins.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Chemotherapy; Procedure: Surgery; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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).
Measured: two months
Assessment of disease progression
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.
Measured: 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.
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.
Measured: 12 months
Assessment of bone marrow condition.
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.
Measured: 24 months
Study the impact of patients treated with Cardioxane in cardioprotection
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2012 (estimated)
- Study start30 Mar 2010
- Primary completion20 Dec 2017
- Study completion18 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Investigacion en Sarcomas
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mariló de Carrillo, Grupo Espanol de Investigacion en Sarcomas
- Investigators
- Jaume Mora Graupera, MD, Study chair, GEIS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01696669
- Sponsor's protocol ID
- GEIS-21
- Other IDs
- 2009-016027-62, 2009
- Status last verified
- Jul 2018
- First submitted
- 30 Jun 2011
- Last updated
- 1 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01696669
- Acronym / sponsor ID
- GEIS-21
- Conditions
- Ewing's Sarcoma
- Keywords
- Ewing's Sarcoma, P6 protocol MSKCC, Gemcitabine, Docetaxel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Grupo Espanol de Investigacion en SarcomasUniversity, hospital or other
- Study start
- 30 Mar 2010 (actual)
- Primary completion
- 20 Dec 2017 (actual)
- Study completion
- 18 Jan 2018 (actual)
- First posted
- 1 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy + Surgery + Radiotherapy | Experimental | Drug: Chemotherapy, Procedure: Surgery, Radiation: RadiotherapyStandard 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. |
Who may qualify
- Ages
- Up to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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%.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemotherapy* 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. | Drug | Chemotherapy + Surgery + Radiotherapy |
| SurgerySurgical intervention aiming to completely resect the tumor with negative margins. | Procedure or surgery | Chemotherapy + Surgery + Radiotherapy |
| RadiotherapyOn 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. | Radiation | Chemotherapy + Surgery + Radiotherapy |
Primary outcome
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.
Assessment of the progression free survival in all the patients enrolled in the study 3 years after the completion of the treatment under study.
5 secondary outcomes
Objective response rate (ORR)
Time frame: two months
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.
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
Assessment of bone marrow condition.
Time frame: 24 months
Study the impact of patients treated with Cardioxane in cardioprotection
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaume Mora Graupera, MD study chair
GEIS
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chemotherapy, Surgery and Radiotherapy in people with Ewing's Sarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 9 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2018.