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

NCT01864109 | Active Not Recruiting Phase 2

• 1 other identifier: 13-068
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 7

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.

Conditions

Newly Diagnosed Ewing Sarcoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  4 years

Secondary Outcomes (2)

• event free survival of patients with metastatic disease

  4 years

• adverse event profile

  2 years

Study Arms (2)

Patients with localized disease

EXPERIMENTAL

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

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

Patients with metastatic disease

EXPERIMENTAL

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)

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

Interventions

Cyclophosphamide DRUG

Patients with localized disease; Patients with metastatic disease

Doxorubicin DEVICE

Patients with localized disease; Patients with metastatic disease

Vincristine DRUG

Patients with localized disease; Patients with metastatic disease

Ifosfamide DRUG

Patients with localized disease; Patients with metastatic disease

Etoposide DRUG

Patients with localized disease; Patients with metastatic disease

Surgery PROCEDURE

Patients with localized disease; Patients with metastatic disease

Temozolomide DRUG

Patients with localized disease; Patients with metastatic disease

Irinotecan DRUG

Patients with localized disease; Patients with metastatic disease

Mesna DRUG

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

Patients with localized disease; Patients with metastatic disease

Dexrazoxane DRUG

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

Patients with localized disease; Patients with metastatic disease

G-CSF DRUG

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

Patients with localized disease; Patients with metastatic disease

Radiation Therapy* RADIATION

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

Patients with localized disease; Patients with metastatic disease

Eligibility Criteria

• Age: 1 Year - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Prior chemotherapy or radiotherapy (other than limited, emergent radiotherapy for treatment of eg. spinal cord compromise or threatened airway)
• Pregnant or breastfeeding females

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Interventions

Cyclophosphamide; Vincristine; Ifosfamide; Etoposide; Surgical Procedures, Operative; Radiotherapy; Temozolomide; Irinotecan; Mesna; Dexrazoxane; Granulocyte Colony-Stimulating Factor

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Oxazines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Therapeutics; Dacarbazine; Triazenes; Imidazoles; Azoles; Camptothecin; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Razoxane; Diketopiperazines; Piperazines; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Emily Slotkin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2013
• First Posted: May 29, 2013
• Study Start: May 1, 2013
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (7)