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

NCT ID: NCT01864109

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2027-05-31

Brief Summary

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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

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Conditions

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Newly Diagnosed Ewing Sarcoma

Keywords

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CYCLOPHOSPHAMIDE (CYTOXAN) DOXORUBICIN/ADRIAMYCIN ETOPOSIDE (VP-16) IFOSFAMIDE IRINOTECAN (CPT-11) CAMPTOSAR TEMOZOLOMIDE VINCRISTINE 13-068

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Intervention Type DEVICE

Vincristine

Intervention Type DRUG

Ifosfamide

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Surgery

Intervention Type PROCEDURE

Radiation Therapy*

Intervention Type RADIATION

If local control includes RT, RT should be given concurrently with chemotherapy cycles

Temozolomide

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Mesna

Intervention Type DRUG

Mesna 2,100 mg/m2 (or 70 mg/kg if \< 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.

Dexrazoxane

Intervention Type DRUG

Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.

G-CSF

Intervention Type DRUG

G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.

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)

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Intervention Type DEVICE

Vincristine

Intervention Type DRUG

Ifosfamide

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Surgery

Intervention Type PROCEDURE

Radiation Therapy*

Intervention Type RADIATION

If local control includes RT, RT should be given concurrently with chemotherapy cycles

Temozolomide

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Mesna

Intervention Type DRUG

Mesna 2,100 mg/m2 (or 70 mg/kg if \< 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.

Dexrazoxane

Intervention Type DRUG

Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.

G-CSF

Intervention Type DRUG

G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.

Interventions

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Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Intervention Type DEVICE

Vincristine

Intervention Type DRUG

Ifosfamide

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Surgery

Intervention Type PROCEDURE

Radiation Therapy*

If local control includes RT, RT should be given concurrently with chemotherapy cycles

Intervention Type RADIATION

Temozolomide

Intervention Type DRUG

Irinotecan

Intervention Type 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.

Intervention Type DRUG

Dexrazoxane

Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.

Intervention Type DRUG

G-CSF

G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

1 Year

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emily Slotkin, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

Countries

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United States

Related Links

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http://www.mskcc.org/

Memorial Sloan-Kettering Cancer Center

Other Identifiers

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13-068

Identifier Type: -

Identifier Source: org_study_id