Irinotecan Hydrochloride, Temozolomide, and Combination Chemotherapy in Treating Patients with Newly Diagnosed Ewing Sarcoma

Status: Active

Description

This phase II trial studies how well irinotecan hydrochloride, temozolomide, and combination chemotherapy work in treating patients with newly diagnosed Ewing sarcoma. Drugs used in chemotherapy, such as irinotecan hydrochloride, temozolomide, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, ifosfamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, or by stopping them from dividing.

Eligibility Criteria

Inclusion Criteria

  • Newly diagnosed, previously untreated patients with histologically or molecularly confirmed Ewing sarcoma
  • Absolute neutrophil count >= 1,000/K/mcL
  • Platelet count >= 100,000/K/mcL
  • Normal creatinine for age: * =< 0.8 mg/dL (age =< 5 years) * =< 1 mg/dL (age 6 to =< 10 years) * =< 1.2 mg/dL (age 11 to =< 15 years) * =< 1.5 mg/dL (age >= 16 years) OR
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 x the ULN (in the absence of hepatic involvement of tumor; patients with hepatic involvement are considered eligible for study)
  • Alanine aminotransferase (ALT) =< 2.5 x the ULN (in the absence of hepatic involvement of tumor; patients with hepatic involvement are considered eligible for study)
  • Shortening fraction >= 28% by echocardiogram OR
  • Left ventricular ejection fraction (LVEF) >= 50% on technetium-99m pertechnetate radionuclide cineangiography (multi gate acquisition scan [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

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Paul A. Meyers
Phone: 212-639-5952

Israel

Jerusalem
Hadassah University Hospital
Status: Approved
Contact: Dror Raviv
Phone: 02-6777408
Email: DRORRA@HADASSAH.ORG.IL

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the effect on event free survival of irinotecan hydrochloride (irinotecan) and temozolomide added to standard therapy of patients with localized disease.

SECONDARY OBJECTIVES:

I. To estimate the effect on event free survival of irinotecan and temozolomide added to standard therapy of patients with metastatic disease.

II. To determine the tolerability and adverse event profile of irinotecan and temozolomide added to standard therapy.

III. To estimate overall survival with the addition of irinotecan and temozolomide to the initial treatment of patients with Ewing sarcoma (ES).

OUTLINE: Patients are assigned to 1 of 2 treatment groups based on disease stage.

GROUP I (localized disease):

COURSES 1-3, 7: Patients receive cyclophosphamide intravenously (IV) over 6 hours* and doxorubicin hydrochloride IV over 15-30 minutes* on days 1-2, and vincristine sulfate IV* over 10 minutes on day 1.

COURSES 4-6: Patients receive ifosfamide IV over 2 hours and etoposide phosphate IV over 1 hour* on days 1-5.

COURSES 8-13: Patients receive irinotecan hydrochloride IV over 1 hour* on days 1-10 and temozolomide orally (PO) or IV* over 90 minutes at the discretion of treating physician on days 1-5.

Treatment repeats every 3 weeks for 13 courses in the absence of disease progression or unacceptable toxicity.

GROUP II (metastatic disease):

COURSES 1-3, 15: Patients receive cyclophosphamide IV over 6 hours* and doxorubicin hydrochloride IV over 15-30 minutes* on days 1-2, and vincristine sulfate IV* over 10 minutes on day 1.

COURSES 4, 5, 7, 8, 10, 11, 13, 14, 16, and 17: Patients receive irinotecan hydrochloride IV over 1 hour* on days 1-10 and temozolomide PO or IV* over 90 minutes at the discretion of treating physician on days 1-5.

COURSES 6, 9, and 12: Patients receive ifosfamide IV over 2 hours and etoposide phosphate IV over 1 hour* on days 1-5.

Treatment repeats every 3 weeks for 17 courses in the absence of disease progression or unacceptable toxicity.

*NOTE: And as clinically indicated.

After completion of study treatment, patients are followed up monthly for 1 year, every 2 months for 1 year, every 4 months for 1 year, and every 6 months for 1 year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Paul A. Meyers

Trial IDs

Primary ID 13-068
Secondary IDs NCI-2013-01094
Clinicaltrials.gov ID NCT01864109