Newly Diagnosed Ewing Sarcoma
Conditions
Keywords
CYCLOPHOSPHAMIDE (CYTOXAN), DOXORUBICIN/ADRIAMYCIN, ETOPOSIDE (VP-16), IFOSFAMIDE, IRINOTECAN (CPT-11) CAMPTOSAR, TEMOZOLOMIDE, VINCRISTINE, 13-068
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.
Interventions
DRUGCyclophosphamide
DEVICEDoxorubicin
DRUGVincristine
DRUGIfosfamide
DRUGEtoposide
PROCEDURESurgery
RADIATIONRadiation Therapy*
If local control includes RT, RT should be given concurrently with chemotherapy cycles
DRUGTemozolomide
DRUGIrinotecan
DRUGMesna
Mesna 2,100 mg/m2 (or 70 mg/kg if \< 10 yrs of age) administered intravenously in concordance with institutional pediatric administration guidelines.
DRUGDexrazoxane
Dexrazoxane 375 mg/m2 intravenously over approximately 15-30 minutes and as clinically indicated. To be administered immediately prior to doxorubicin.
DRUGG-CSF
G-CSF-to be administered after the completion of appropriate chemotherapy cycles as per institutional guidelines.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| event free survival of patients with localized disease | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| event free survival of patients with metastatic disease | 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 | 2 years | Toxicities are graded by the Common Toxicity Criteria (Version 4.0) developed by the National Cancer Institute (NCI) of the USA. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREmily Slotkin, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed