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NCT Number: NCT02063022

Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma

Controlled, randomized phase III study, with the intent of optimizing the treatment of not metastatic Ewing Sarcoma. The patients will be randomized into 2 arms: standard treatment vs intensive treatment. Both arms will receive an induction treatment followed by surgery (wherever is possible) and/or radiotherapy. The maintenance treatment will be different on the basis of the response to the induction treatment (good or poor)

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Key information

Conditions

Ewing's Sarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Osteosarcoma Sarcoma Sarcoma, Ewing

Age range

Up to 40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro di Riferimento Oncologico - Unit of Medical Oncology, Aviano, Pordenone, Italy

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About this study

Eligible patients with non metastatic Ewing's Sarcoma will be randomized into 2 different arms: standard treatment arm A (based on the ISG/SSG III protocol) or into the experimental arm B(chemotherapy with dose intensification and shorter length of treatment).

Both arm will receive an induction treatment with higher dose intensity of doxorubicin and ifosfamide in Arm B.

After the induction treatment all the patient will undergo to local treatment (surgery and/or radiotherapy)that will be followed by a maintenance therapy.

The maintenance therapy will be different for both arms and, within each arm, on the basis of the response (histologically evaluated) of the pre-local treatment therapy.

Maintenance for Arm A: Poor responders will undergo to stem cells apheresis and their reinfusion after treatment with high doses of Busulfan and Melphalan 25 weeks.

Good responders will receive a 6 drugs maintenance treatment for 37 weeks (as per standard ISG/SSG III protocol)

Maintenance for Arm B: Poor responders will undergo to stem cells apheresis and their reinfusion after an intensified treatment with high doses of Busulfan and Melphalan (25 weeks).

Good responders will receive a maintenance treatment for 25 weeks

The primary aim of the study is to assess the Event Free Survival (EFS) that is expected to be similar in both arms

The secondary objectives are:

To assess if the induction treatment in Arm B is able to increase the percentage of good responders compared to those who receive standard treatment.

To assess the toxicity and the Quality of Life related to the chemotherapy treatment

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Ewing Sarcoma or PNET diagnosis centrally confirmed
  • Age ≤ 40 years
  • Absence of evident metastasis or lung met < 0.5 cm Presence of skip metastasis in the bone compartment of the primary tumor is to be considered as local disease and not metastatic.
  • Adeguate bone marrow, hepatic and renal function
  • Left Ventricular Ejection Fraction > 50%
  • No primary Ewing Sarcoma treatments (both chemotherapy and/or radiotherapy)
  • Voluntarily signed an informed consent form
  • Radiological and histological documentation available for central review.

Exclusion criteria

  • Presence of lung or extra-pulmonary lesions
  • Bone Marrow involvement
  • In case of chest disease: presence of plural effusion
  • Elapsed time between histological diagnosis and chemotherapy start, more than 4 weeks
  • Any medical contraindication to the use of the study drugs
  • Any psychological or social conditions that can compromise the protocol compliance and/or follow-up
  • Previous malignancies (excluded in situ cervix carcinoma)

Treatment and study plan

Standard treatment (as per protocol ISG SSG III)

Drug

Induction treatment with: 4 cycle of Vincristine (9mg/,2), Dactinomycin (6mg/m2), Doxorubicin (160mg/m2), Cyclophosphamide (2.4g/m2), Ifosfamide (18g/M2) and Etoposide (450mg/m2) given every 3 weeks Maintenance treatment for poor responder (25 weeks): Vincristine (12mg/m2), Dactinomycin (1.5mg/m2), Doxorubicin (320mg/m2), Ifosfamide (27g/m2), Cyclophosphamide (8.8g/m2), Etoposide (1.5g/m2) and peripheral Cells Steam Transplant after Busulfan and Melphalan treatment Maintenance treatment (37 week) for good responder: Vincristine (18mg/m2), Dactinomycin (6mg/m2), Doxorubicin (400mg/m2), Ifosfamide (72g/m2), Cyclosphosphamide(6g/m2), Etoposide (1.8 g/m2)

Other names: Vincristine, Dactinomycin, Doxorubicin, Ifosfamide, Cyclophosphamide, Etoposide, Busulfan, Melphalan

Intensified chemotherapy

Drug
  • Induction treatment with: 4 cycle of Vincristine (10.5 mg/m2), Doxorubicin (320 mg/m2) and Ifosfamide (36 mg/m2) given every 3 weeks
  • Maintenance treatment for poor responder (25 weeks): Vincristine (12mg/m2), Doxorubicin (400mg/m2), Ifosfamide (63g/m2), Cyclophosphamide (4g/m2), Etoposide (1.5g/m2) and Cells Steam Transplant after Busulfan and Melphalan treatment
  • Maintenance treatment (25 week) for good responder: Vincristine (12mg/m2), Doxorubicin (400mg/m2), Ifosfamide (72g/m2), Etoposide (1.8g/m2)

Other names: Vincristine,, Doxorubicin, Ifosfamide, Cyclophosphamide, Etoposide, Busulfan, Melphalan

Primary outcomes

  1. Event Free Survival (EFS)

    Time frame: 5 years

    The EFS (event defined as Progressive Disease , onset of local relapse and/or metastasis, death due to chemotherapy toxicity or for other causes) will be calculated from the first treatment day up to the event onset or to last follow-up

Secondary outcomes

  1. Disease Free Survival (DFS)

    Time frame: expected average 3 years

    The DFS will be calculated from the day that the patient will be free from disease (surgery date and/or radiotherapy completion) up to the date of progression disease or last follow-up

  2. Metastasis Free Survival

    Time frame: expected average 2 years

    The Metastasis free Survival will be evaluated from the time of disease free (surgery performed and/or radiotherapy completed) to the onset of distance metastasis or last follow-up

  3. Overall Survival (OS)

    Time frame: expected average 5 years

    The OS will be evaluated for the start treatment day to the day of death (for any causes)

Sponsors and collaborators

Lead sponsor

Italian Sarcoma Group

Network

Registry information

Official study title

Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.

Acronym: EW-1

Important dates

Study start
2009
Primary completion
2022
Study completion
2022
First posted
Feb 14, 2014
Registry last updated
Sep 19, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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