Back to resultsIrinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma
Primary Purpose
Newly Diagnosed Ewing Sarcoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Doxorubicin
Vincristine
Ifosfamide
Etoposide
Surgery
Radiation Therapy*
Temozolomide
Irinotecan
Mesna
Dexrazoxane
G-CSF
Sponsored by
About this trial
This is an interventional treatment trial for Newly Diagnosed Ewing Sarcoma focused on measuring CYCLOPHOSPHAMIDE (CYTOXAN), DOXORUBICIN/ADRIAMYCIN, ETOPOSIDE (VP-16), IFOSFAMIDE, IRINOTECAN (CPT-11) CAMPTOSAR, TEMOZOLOMIDE, VINCRISTINE, 13-068
Eligibility Criteria
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
Sites / Locations
- Memorial Sloan Kettering Cancer CenterRecruiting
- Memorial Sloan Kettering MonmouthRecruiting
- Memorial Sloan Kettering BergenRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Memorial Sloan Kettering NassauRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Patients with localized disease
Patients with metastatic disease
Arm Description
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
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)
Outcomes
Primary Outcome Measures
event free survival of patients with localized disease
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.
Secondary Outcome Measures
event free survival of patients with metastatic disease
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
Toxicities are graded by the Common Toxicity Criteria (Version 4.0) developed by the National Cancer Institute (NCI) of the USA.
Full Information
NCT ID
NCT01864109
First Posted
May 23, 2013
Last Updated
September 15, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT01864109
Brief Title
Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2013 (undefined)
Primary Completion Date
May 2027 (Anticipated)
Study Completion Date
May 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Newly Diagnosed Ewing Sarcoma
Keywords
CYCLOPHOSPHAMIDE (CYTOXAN), DOXORUBICIN/ADRIAMYCIN, ETOPOSIDE (VP-16), IFOSFAMIDE, IRINOTECAN (CPT-11) CAMPTOSAR, TEMOZOLOMIDE, VINCRISTINE, 13-068
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
93 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients with localized disease
Arm Type
Experimental
Arm Description
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
Arm Title
Patients with metastatic disease
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Type
Device
Intervention Name(s)
Doxorubicin
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Type
Drug
Intervention Name(s)
Ifosfamide
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy*
Intervention Description
If local control includes RT, RT should be given concurrently with chemotherapy cycles
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Type
Drug
Intervention Name(s)
Mesna
Intervention Description
Mesna 2,100 mg/m2 (or 70 mg/kg if < 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.
Intervention Type
Drug
Intervention Name(s)
Dexrazoxane
Intervention Description
Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.
Primary Outcome Measure Information:
Title
event free survival of patients with localized disease
Description
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.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
event free survival of patients with metastatic disease
Description
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.
Time Frame
4 years
Title
adverse event profile
Description
Toxicities are graded by the Common Toxicity Criteria (Version 4.0) developed by the National Cancer Institute (NCI) of the USA.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emily Slotkin, MD
Phone
212-639-8856
First Name & Middle Initial & Last Name or Official Title & Degree
Paul Meyers, MD
Phone
212-639-5952
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
212-639-8856
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily MD, MD
Phone
212-639-8856
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
212-639-8856
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
212-639-8856
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
212-639-8856
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
212-639-8856
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Phone
212-639-8856
12. IPD Sharing Statement
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan-Kettering Cancer Center
Learn more about this trial
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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