RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as thrombopoietin and G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of colony-stimulating factors in treating children who have recurrent or refractory solid tumors and who are receiving chemotherapy.

Condition	Treatment or Intervention	Phase
Brain Tumors Musculoskeletal Tumors Kidney Tumors Solid Tumors	Drug: carboplatin  Drug: etoposide  Drug: filgrastim  Drug: ifosfamide  Drug: recombinant human thrombopoietin	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin in children with solid tumors receiving myelosuppressive chemotherapy with ifosfamide, carboplatin, and etoposide (ICE).

II. Determine a safe dose of recombinant human thrombopoietin with filgrastim (G-CSF) in this patient population.

III. Evaluate the time to platelet count recovery following chemotherapy in this patient population.

IV. Evaluate the depth and duration of neutropenia and thrombocytopenia and the number of platelet transfusion events in this patient population.

PROTOCOL OUTLINE: This is a dose escalation study of recombinant human thrombopoietin.

All patients receive chemotherapy consisting of carboplatin IV over 60 minutes on days 0 and 1 and etoposide and ifosfamide IV over 60 minutes on days 0-4. Chemotherapy is continued in the absence of disease progression or unacceptable toxicity for a maximum of 6 courses every 21 days.

Cohorts of 3-6 patients each receive escalating doses of recombinant human thrombopoietin IV on days 4, 6, 8, 10, and 12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which fewer than 2 patients experience dose limiting toxicity. After the MTD is determined an additional cohort of patients are treated at this dose level every other day on days 4-20. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until absolute neutrophil count is greater than 1000/mm3 for 2 consecutive days or day 33.

PROJECTED ACCRUAL: A total of 24 evaluable patients will be accrued for this study.

Ages Eligible for Study:  1 Year   -   21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven (except for brain stem tumors) malignancy that has failed or relapsed after standard first-line antineoplastic therapy; Sarcoma (soft tissue and bone); Kidney tumors; Brain tumors; Other solid tumors (gonadal and germ cell tumors, malignant melanoma, retinoblastoma, liver tumors, and miscellaneous tumors)
• Must have had recurrence within the past 4 weeks
• No bone marrow involvement
• No prior or concurrent myelogenous leukemia

--Prior/Concurrent Therapy--

• Biologic therapy: At least 10 days since prior colony-stimulating factor therapy and recovered; At least 30 days since prior epoetin alfa; No other concurrent cytokines, including epoetin alfa
• Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered; At least 3 months since therapy with etoposide, carboplatin, or ifosfamide that is identical to study treatment
• Endocrine therapy: Not specified
• Radiotherapy: Concurrent radiotherapy allowed after third course of therapy; No prior cranial/spinal radiotherapy; No prior radiotherapy to greater than 50% of bone marrow
• Surgery: Concurrent surgery allowed after the second course of therapy
• Other: No concurrent investigational agents; No concurrent lithium, aspirin, coumadin, or heparin

--Patient Characteristics--

• Age: 1 to 21
• Performance status: Lansky or Karnofsky 60-100%
• Life expectancy: At least 12 weeks
• Hematopoietic: Absolute neutrophil count greater than 1000/mm3; Platelet count greater than 100,000/mm3; No grade III or IV thrombosis
• Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN); SGOT or SGPT less than 2.5 times ULN
• Renal: Creatinine clearance or glomerular filtration rate at least 70 mL/min
• Cardiovascular: Ejection fraction normal; No evidence of arrhythmias requiring therapy; Fractional shortening greater than 28%
• Other: Not pregnant or nursing

California
      Beckman Research Institute, City of Hope, Los Angeles,  California,  91010,  United States
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92668,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Long Beach Memorial Medical Center, Long Beach,  California,  90806,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5265,  United States
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Children's Mercy Hospital - Kansas City, Kansas City,  Missouri,  64108,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      Kaplan Cancer Center, New York,  New York,  10016,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Tennessee
      Vanderbilt Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84132,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia

Study chairs or principal investigators

Mitchell S. Cairo,  Study Chair,  Children's Cancer Group   

Study ID Numbers:  CDR0000066668; CCG-09717
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003597
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08