Clinical trial NCT00470275: Cytarabine in Treating Young Patients With Recurrent or Refractory Ewing's Sarcoma
Official title: Phase II Trial of Intermediate-Dose Cytarabine to Modulate EWS/FLI for Children and Young Adults With Recurrent or Refractory Ewing Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-07
Enrollment: 10
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well cytarabine works in treating young patients with recurrent or refractory Ewing's sarcoma.

Detailed description: OBJECTIVES:

* Determine the response rate in younger patients with recurrent or refractory Ewing's sarcoma treated with cytarabine.

OUTLINE: This is a multicenter study.

Patients receive cytarabine IV over 2 hours twice daily on days 1-5. Treatment repeats every 21 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed Ewing's sarcoma or primitive neuroectodermal tumor (PNET)
* Disease that has recurred or not responded despite prior therapy

  * Has declined enrollment on or is not eligible for clinical trial COG-AEWS0521
* Must have at least one site of measurable disease involving lung or soft tissue as documented by CT scan and/or MRI
* No disease limited to bone

PATIENT CHARACTERISTICS:

* Karnofsky performance status (PS) 50-100% (for patients \> 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
* Life expectancy ≥ 8 weeks
* ANC ≥ 750/mm\^3
* Platelet count ≥ 75,000/mm\^3 (50,000/mm\^3 if documented bone marrow metastatic disease) (transfusion independent)
* Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed)
* Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age and \< 2.0 mg/dL
* ALT ≤ 2.5 times ULN
* Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR creatinine meeting the following criteria:

  * ≤ 0.4 mg/dL (1 month to \< 6 months of age)
  * ≤ 0.5 mg/dL (6 months to \< 1 year of age)
  * ≤ 0.6 mg/dL (1 to \< 2 years of age)
  * ≤ 0.8 mg/dL (2 to \< 6 years of age)
  * ≤ 1.0 mg/dL (6 to \< 10 years of age)
  * ≤ 1.2 mg/dL (10 to \< 13 years of age)
  * ≤ 1.4 mg/dL (≥ 13 years of age) (female)
  * ≤ 1.5 mg/dL (13 to \< 16 years of age) (male)
  * ≤ 1.7 mg/dL (≥ 16 years of age) (male)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection, including systemic fungal infections requiring ongoing antifungal therapy

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from all prior tumor-directed therapy
* At least 7 days since prior biologic therapy or immunotherapy
* At least 1 week since prior hematopoietic growth factors (2 weeks for pegfilgrastim)
* At least 2 weeks since prior myelosuppressive chemotherapy
* At least 2 weeks since prior local palliative (small-port) radiotherapy
* At least 6 weeks since prior substantial bone marrow radiotherapy
* At least 6 months since prior radiotherapy to ≥ 50% of the pelvis
* At least 6 months since prior autologous stem cell transplantation
* No prior allogeneic stem cell transplantation
* No prior cytarabine
* No other concurrent investigational agents, including chemotherapy, immunotherapy, or biologic therapy
* No other concurrent anticancer chemotherapy or immunomodulating agents

  * Concurrent corticosteroids allowed
* No concurrent intrathecal chemotherapy
* Concurrent radiotherapy to localized painful lesions allowed provided at least one measurable lesion is not irradiated (no irradiated lesion may be used to assess tumor response)

Primary outcomes:
measure: Response
timeFrame: the first six cycles of study chemotherapy (126 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Farmington
country: United States
facility: Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
state: Connecticut
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Cancer Institute at St. Joseph's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Kaplan Cancer Center at St. Mary's Medical Center
state: Florida
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Springfield
country: United States
facility: Simmons Cooper Cancer Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis
state: Missouri
city: Las Vegas
country: United States
facility: Sunrise Hospital and Medical Center
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Morristown
country: United States
facility: Overlook Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Columbus Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Children's Medical Center - Dayton
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center and Children's Hospital
state: Oregon
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital Comprehensive Cancer Center
state: Rhode Island
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health South Carolina Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center School of Medicine - Amarillo
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Charleston
country: United States
facility: West Virginia University Health Sciences Center - Charleston
state: West Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: Santurce
country: Puerto Rico
facility: San Jorge Children's Hospital
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Kimberly Stegmaier, MD
role: STUDY_CHAIR
affiliation: Dana-Farber Cancer Institute
name: Holcombe E. Grier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: DuBois SG, Krailo MD, Lessnick SL, Smith R, Chen Z, Marina N, Grier HE, Stegmaier K; Children's Oncology Group. Phase II study of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009 Mar;52(3):324-7. doi: 10.1002/pbc.21822.