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Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma

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ClinicalTrials.gov Identifier: NCT01864109
Recruitment Status : Recruiting
First Posted : May 29, 2013
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE May 23, 2013
First Posted Date  ICMJE May 29, 2013
Last Update Posted Date July 15, 2021
Study Start Date  ICMJE May 2013
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2013)
event free survival of patients with localized disease [ Time Frame: 4 years ]
We will determine event free survival from the time of study entry for all patients. An event would include death from any cause, progression of tumor, recurrence of tumor, or second malignancy. Progressive disease (PD) will be defined according to RECIST 1.1.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2013)
  • event free survival of patients with metastatic disease [ Time Frame: 4 years ]
    We will determine event free survival from the time of study entry for all patients. An event would include death from any cause, progression of tumor, recurrence of tumor, or second malignancy. Progressive disease (PD) will be defined according to RECIST 1.1.
  • adverse event profile [ Time Frame: 2 years ]
    Toxicities are graded by the Common Toxicity Criteria (Version 4.0) developed by the National Cancer Institute (NCI) of the USA.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma
Official Title  ICMJE A Phase II Trial of Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma
Brief Summary

The purpose of this study is to find out what effects, good and/or bad, the combination of irinotecan and temozolomide has on Ewing sarcoma.

Irinotecan and temozolomide are chemotherapy drugs that are used very often to treat pediatric patients at MSKCC. The investigators have used these two drugs for many years to treat patients with Ewing sarcoma whose cancer has relapsed.

For patients with newly diagnosed Ewing sarcoma the current standard of care at MSKCC is a five drug chemotherapy regimen in combination with surgery and/or radiation therapy. This standard regimen is called the EFT regimen. . Some patients with Ewing sarcoma do not have their cancer cured by the chemotherapy and surgery/radiation therapy.

This study adds the chemotherapy drugs called irinotecan and temozolomide to the standard EFT regimen. The investigators are trying to improve the success of standard therapy by adding these drugs. The use of irinotecan and temozolomide in this study is experimental because they have not been used before in patients with newly diagnosed Ewing sarcoma. However the investigators have found these drugs to be effective in patients with relapsed Ewing sarcoma. It is not known if adding these two drugs will improve the outcomes of patients treated for Ewing sarcoma.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Newly Diagnosed Ewing Sarcoma
Intervention  ICMJE
  • Drug: Cyclophosphamide
  • Device: Doxorubicin
  • Drug: Vincristine
  • Drug: Ifosfamide
  • Drug: Etoposide
  • Procedure: Surgery
  • Radiation: Radiation Therapy*
    If local control includes RT, RT should be given concurrently with chemotherapy cycles
  • Drug: Temozolomide
  • Drug: Irinotecan
  • Drug: Mesna
    Mesna 2,100 mg/m2 (or 70 mg/kg if < 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.
  • Drug: Dexrazoxane
    Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.
  • Drug: G-CSF
    G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.
Study Arms  ICMJE
  • Experimental: Patients with localized disease

    Patients with localized disease will receive six cycles of the combination as "maintenance" therapy following standard chemotherapy.

    • Cycles 4-6 will include:

      • Ifosfamide 2,800 mg/m2/day on days 1-5
      • Etoposide 100 mg/m2/day on days 1-5
    • Cycle 7 will include :

      • Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients < 10 years of age at a dose of 70 mg/kg/day
      • Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day
      • Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)
    • Cycles 8-13 will include:

      • Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously
      • Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously
    Interventions:
    • Drug: Cyclophosphamide
    • Device: Doxorubicin
    • Drug: Vincristine
    • Drug: Ifosfamide
    • Drug: Etoposide
    • Procedure: Surgery
    • Radiation: Radiation Therapy*
    • Drug: Temozolomide
    • Drug: Irinotecan
    • Drug: Mesna
    • Drug: Dexrazoxane
    • Drug: G-CSF
  • Experimental: Patients with metastatic disease

    Patients will get 10 cycles of the combination intercalated between the final 4 cycles of standard chemotherapy.

    • Cycles 4, 5, 7, 8, 10, 11, 13, 14, 16, and 17 will include:

      • Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously
      • Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously
    • Cycles 6, 9, and 12 will include:

      • Ifosfamide 2,800 mg/m2/day on days 1-5
      • Etoposide 100 mg/m2/day on days 1-5
    • Cycle 15 will include:

      • Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients < 10 years of age at a dose of 70 mg/kg/day
      • Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day
      • Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)
    Interventions:
    • Drug: Cyclophosphamide
    • Device: Doxorubicin
    • Drug: Vincristine
    • Drug: Ifosfamide
    • Drug: Etoposide
    • Procedure: Surgery
    • Radiation: Radiation Therapy*
    • Drug: Temozolomide
    • Drug: Irinotecan
    • Drug: Mesna
    • Drug: Dexrazoxane
    • Drug: G-CSF
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2018)
93
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2013)
83
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age greater than or equal to one year and less than or equal to 40 years at the time of diagnosis
  • Newly diagnosed, previously untreated patients with histologically or molecularly confirmed Ewing sarcoma
  • Adequate hematologic function:
  • Absolute neutrophil count ≥ 1,000/K/mcl
  • Platelet count ≥ 100,000/Kmcl
  • Adequate renal function:
  • Normal creatinine for age (See table below) OR
  • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 Age(Years) Maximum Serum Creatinine (mg/dL) ≤ 5 0.8 6 to ≤ 10 1 11 to ≤ 15 1.2 ≥ 16 1.5

Adequate hepatic function:

  • Total bilirubin ≤ 1.5 x the ULN
  • AST ≤ 2.5 x the ULN [in the absence of hepatic involvement of tumor. Patients with hepatic involvement are considered eligibile for study]
  • ALT ≤ 2.5 x the ULN [in the absence of hepatic involvement of tumor. Patients with hepatic involvement are considered eligibile for study]

Normal cardiac function:

  • Shortening fraction ≥ 28% by echocardiogram OR
  • Left ventricular ejection fraction (LVEF) ≥ 50% on technetium- 99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram
  • Patients must consent to an indwelling central venous catheter.
  • Sexually active patients of reproductive potential must be willing to use an effective method of contraception.

Exclusion Criteria:

  • Prior chemotherapy or radiotherapy (other than limited, emergent radiotherapy for treatment of eg. spinal cord compromise or threatened airway)
  • Pregnant or breastfeeding females
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paul Meyers, MD 212-639-5952
Contact: Emily Slotkin, MD 212-639-8856
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01864109
Other Study ID Numbers  ICMJE 13-068
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul Meyers, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP